3/30/23, 12:43 AM 6878

Official reprint from UpToDate®

www.uptodate.com © 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Clinical manifestations and evaluation of edema in adults

Author: C Christopher Smith, MD
Section Editors: Mark D Aronson, MD, Michael Emmett, MD
Deputy Editor: Jane Givens, MD, MSCE

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Feb 2023. | This topic last updated: Mar 17, 2023.

INTRODUCTION

Edema is defined as a palpable swelling produced by expansion of the interstitial fluid volume;
when massive and generalized, the excess fluid accumulation is called anasarca. A variety of
clinical conditions are associated with the development of edema, including heart failure,
cirrhosis, and the nephrotic syndrome, as well as local conditions such as venous and lymphatic
disease ( table 1). (See "Pathophysiology and etiology of edema in adults".)

The clinical features and evaluation of generalized edematous states in adults are reviewed
here. The general principles of the treatment of edema in adults, including the use of diuretics
to remove the excess fluid, the treatment of refractory edema, and the approach to edema in
children, are discussed separately. (See "General principles of the treatment of edema in adults"
and "Causes and treatment of refractory edema in adults" and "Evaluation and management of
edema in children".)

OVERVIEW OF PATHOPHYSIOLOGY

The pathophysiology and etiology of edema formation are discussed in detail elsewhere (see
"Pathophysiology and etiology of edema in adults"), but the pathophysiology is briefly reviewed
here.

An increase in interstitial fluid volume that could lead to edema does not occur in normal
subjects because of the tight balance of hemodynamic forces along the capillary wall and the
function of the lymphatic vessels. For generalized edema to occur, two factors must be present:

https://www.uptodate.com/contents/6878/print 1/27
3/30/23, 12:43 AM 6878

● An alteration in capillary hemodynamics that favors the movement of fluid from the
vascular space into the interstitium. Such movement requires a change in one or more
components of Starling's law: increased capillary hydrostatic pressure, decreased capillary
oncotic pressure (ie, hypoalbuminemia), and/or increased capillary permeability. (See
"Pathophysiology and etiology of edema in adults", section on 'Capillary hemodynamics'.)

● The retention of dietary or intravenously administered sodium and water by the kidneys.
Edema (other than localized edema as with an allergic reaction) does not become clinically
apparent until the interstitial volume has increased by 2.5 to 3 L, an amount that is almost
equal to the plasma volume. Thus, patients would develop marked hemoconcentration
and shock if the plasma volume were not maintained by renal retention of sodium and
water to compensate for the shift of fluid to the interstitium.

The retention of sodium and water can either be a primary event, as in renal failure, or a
secondary event resulting from a primary reduction in either cardiac output (as in heart failure)
or systemic vascular resistance (as in cirrhosis). In the latter settings, fluid retention tends to
return the effective circulating volume toward normal. Diuretic therapy in such patients may
have a deleterious effect on systemic hemodynamics even though it reduces the edema. Thus,
careful monitoring is required. (See "General principles of the treatment of edema in adults",
section on 'What are the consequences of the removal of edema fluid?'.)

CLINICAL MANIFESTATIONS AND EVALUATION

Edema in adults can be divided into peripheral edema, pulmonary edema, ascites, and other
forms of edema, which include lymphedema, nonpitting edema, and periorbital and scrotal
edema.

Peripheral edema — Peripheral edema can be pitting or nonpitting. Pitting edema is more
common and is defined by the presence of tissue depression after pressure is applied to the
edematous area for at least five seconds ( picture 1) [1]. Pitting reflects movement of the
excess interstitial water in response to pressure. Nonpitting edema suggests lymphatic
obstruction or hypothyroidism. (See 'Nonpitting edema' below.)

Although clinicians commonly grade pitting edema from 1+ to 4+ (mild to severe), there is no
agreed-upon definition of these grades. However, this type of grading scheme may help the
clinician record relative changes in edema (eg, less edema after diuretic therapy). Documenting
weight loss is another component of monitoring the efficacy of diuretic therapy.

https://www.uptodate.com/contents/6878/print 2/27
3/30/23, 12:43 AM 6878

Since peripheral edema locates preferentially in the dependent areas, it is primarily found in the
lower extremities in ambulatory patients and over the sacrum in patients confined to bed rest.
Less commonly, peripheral edema may occur in the upper extremities. (See 'Arm edema' below.)

Leg edema — Our approach to the differential diagnosis of leg edema in adults depends upon
whether the patient has unilateral/asymmetric edema or bilateral edema, and upon the acuity
of the edema.

Acute onset of unilateral leg edema raises concern for deep vein thrombosis (DVT), which must
be addressed promptly. (See "Clinical presentation and diagnosis of the nonpregnant adult with
suspected deep vein thrombosis of the lower extremity", section on 'Suspected first DVT (risk
stratification)'.)

Bilateral edema is particularly frequent in older adults and is usually chronic rather than acute.
It is often due to chronic venous disease, heart failure, venodilating medications, or pulmonary
hypertension (the most commonly missed cause of bilateral edema). The list of etiologies for
bilateral edema is extensive ( table 2).

Certain infiltrative conditions may be mistaken for edema, such as pretibial myxedema seen
with thyroid disease and lipedema (a familial bilateral deposition of excess fat in the lower
extremities). (See "Pretibial myxedema (thyroid dermopathy) in autoimmune thyroid disease".)

Patients with unilateral or asymmetric leg edema

Acute unilateral or asymmetric edema — It is essential to consider the diagnosis of

DVT in patients with acute unilateral or asymmetric leg edema. In addition to edema, patients
with a DVT can have calf tenderness, pain or firmness along the course of a vein, or unilateral
warmth or erythema. A larger calf circumference in the affected leg is the most useful finding,
whereas Homans’ sign (calf pain upon passive dorsiflexion of the foot) is not a reliable sign of
DVT. The findings of DVT may be subtle; patients may present with only unilateral or
asymmetric edema. (See "Clinical presentation and diagnosis of the nonpregnant adult with
suspected deep vein thrombosis of the lower extremity", section on 'Clinical presentation'.)

Acute leg swelling may appear asymmetric in patients who have baseline unilateral or
asymmetric chronic venous disease. In such patients, causes of acute bilateral edema (eg, drug-
induced edema, heart failure) may present with asymmetric leg swelling.

Our approach to patients with acute unilateral or asymmetric leg edema is as follows:

● First, determine the clinical probability of DVT and perform appropriate diagnostic testing
depending upon the clinical probability. The Wells score (calculator 1) and modified Wells
https://www.uptodate.com/contents/6878/print 3/27
3/30/23, 12:43 AM 6878

score (calculator 2) are the best-studied prediction rules. We prefer approaches that
combine an assessment of the clinical probability with D-dimer testing in select patients.
(See "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep
vein thrombosis of the lower extremity", section on 'Suspected first DVT (risk
stratification)'.)

● If DVT has been ruled out based upon the results of testing, it is important to evaluate for
other causes of acute unilateral or asymmetric leg edema. DVT is not present in more than
three-quarters of patients with suspected DVT. In 160 such patients, after exclusion of DVT,
the following causes of leg swelling were identified [2,3]:

• Muscle strain, tear, or twisting injury to the leg – 40 percent

• Leg swelling in a paralyzed limb – 9 percent
• Lymphangitis or lymph obstruction – 7 percent
• Venous insufficiency – 7 percent
• Popliteal (Baker's) cyst – 5 percent
• Cellulitis – 3 percent
• Knee abnormality – 2 percent
• Unknown – 26 percent

Many of these diagnoses are suspected based upon clinical features:

• Calf muscle pull or tear – An inciting injury may be identified in the history, and there
may be signs of bleeding (if ultrasonography is performed) or bruising at the ankle.
The diagnostic evaluation of patients with a suspected calf muscle pull or tear is
presented elsewhere. (See "Calf injuries not involving the Achilles tendon".)

• Cellulitis – Bacterial cellulitis is a common condition of the leg, particularly in patients

who have chronic leg swelling due to venous insufficiency or lymphedema. In bacterial
cellulitis, the warmth and redness often skip areas and may be associated with
constitutional symptoms including fever. Some patients with venous insufficiency
develop a low-grade, nonbacterial cellulitis, which resembles infectious cellulitis, but
without constitutional symptoms. Although fever increases the suspicion for cellulitis, it
can also be present in DVT. The approach to patients with suspected cellulitis is
discussed separately. (See "Cellulitis and skin abscess: Epidemiology, microbiology,
clinical manifestations, and diagnosis".)

• Superficial thrombophlebitis – Superficial vein thrombophlebitis classically presents

with palpable, tender superficial veins. However, since superficial thrombophlebitis is a

https://www.uptodate.com/contents/6878/print 4/27
3/30/23, 12:43 AM 6878

risk factor for DVT, many such individuals also undergo ultrasound to exclude DVT. (See
"Superficial vein thrombosis and phlebitis of the lower extremity veins".)

• Popliteal (Baker's) cyst – The majority of popliteal cysts are due to either distention of a
bursa by fluid originating from a knee joint or posterior herniation of the joint capsule
due to increased intraarticular pressure. A popliteal cyst that causes calf symptoms is
usually leaking or has ruptured. It is often distinguished from DVT by posterior knee
pain, knee stiffness, swelling or a mass behind the knee (especially with the knee in
extension), and bruising around the ankle. However, calf symptoms are common; in
addition, compression of the popliteal vein may cause leg swelling or secondary DVT.
Evaluation of patients with a suspected popliteal cyst is presented elsewhere. (See
"Popliteal (Baker's) cyst".)

• Inflammatory pathology of the knee – Pain, inflammation, and swelling can accompany
any knee joint pathology and may be confused with a popliteal cyst or DVT. (See
"Approach to the adult with unspecified knee pain".)

• May-Thurner syndrome – May-Thurner syndrome occurs in younger females (second or

third decade) who present with acute pain and swelling of the entire left lower
extremity, with or without venous thrombosis. The syndrome is most often caused by a
compression of the left iliac vein between the overlying right common iliac artery and
the fifth lumbar vertebrae. (See "May-Thurner syndrome".)

Chronic unilateral or asymmetric edema — The most common cause of chronic

unilateral or asymmetric edema is lower extremity chronic venous disease. (See "Clinical
manifestations of lower extremity chronic venous disease" and "Diagnostic evaluation of lower
extremity chronic venous insufficiency" and "Overview of lower extremity chronic venous
disease".)

Less common causes include primary or secondary lymphedema, a pelvic neoplasm

compromising venous return, and complex regional pain syndrome. (See "Clinical features and
diagnosis of peripheral lymphedema" and "Complex regional pain syndrome in adults:
Pathogenesis, clinical manifestations, and diagnosis".)

Our approach to patients with chronic unilateral or asymmetric leg edema is as follows:

● Chronic venous disease, lymphedema, and complex regional pain syndrome can generally
be diagnosed based upon clinical features. Such patients do not usually require additional
diagnostic testing or imaging. Suggestive history and physical examination findings
include:
https://www.uptodate.com/contents/6878/print 5/27
3/30/23, 12:43 AM 6878

• Chronic venous disease – There may be an antecedent history of thrombophlebitis in

the affected leg. If the edema is longstanding, it often leads to characteristic
pigmentary changes and skin ulceration ( picture 2). (See "Clinical manifestations of
lower extremity chronic venous disease".)

• Lymphedema – Patients with lymphedema may have a history of an ipsilateral inguinal

or pelvic lymph node dissection, or of radiation therapy. The edema is initially pitting,
but becomes non-pitting as cutaneous fibrosis occurs. (See "Clinical features and
diagnosis of peripheral lymphedema".)

• Complex regional pain syndrome – Complex regional pain syndrome usually occurs
four to six weeks after limb trauma and is characterized by pain, edema, and alteration
in skin color and temperature ( picture 3). Specific diagnostic criteria are presented
elsewhere. (See "Complex regional pain syndrome in adults: Pathogenesis, clinical
manifestations, and diagnosis", section on 'Clinical diagnostic criteria'.)

● If the history and examination are not consistent with venous insufficiency, lymphedema,
or complex regional pain syndrome, compression ultrasonography (CUS) with Doppler
should be obtained. CUS can provide the following information:

• Confirmation of lower extremity chronic venous disease

• Suggestion of pelvic outflow obstruction

A normal study is consistent with either lymphedema or complex regional pain syndrome.

● A neoplasm should be suspected when CUS is suggestive of pelvic outflow obstruction,

particularly in patients with a history of cancer or concerning symptoms such as
unexplained weight loss. If a neoplasm is suspected, imaging of the pelvis should be
obtained. Specifically, if ovarian or endometrial cancer is suspected, a transvaginal
ultrasound should be performed. Otherwise, a contrast-enhanced computed tomography
(CT) scan of the pelvis is preferred.

A pelvic neoplasm can cause unilateral or asymmetric leg edema by compressing the veins
or lymphatic system. The most common etiologies include ovarian cancer, endometrial
cancer, bladder cancer, lymphoma, and prostate cancer. Rarely, benign lesions such as
uterine fibroids or ovarian cysts can cause unilateral leg swelling.

Patients with bilateral leg edema

Acute bilateral leg edema — Acute bilateral leg edema is uncommon. The most likely
etiologies include:
https://www.uptodate.com/contents/6878/print 6/27
3/30/23, 12:43 AM 6878

● Side effect of medications, especially dihydropyridine calcium channel blockers ( table 3)

(see "Major side effects and safety of calcium channel blockers", section on 'Edema')

● Acute heart failure (see "Approach to diagnosis and evaluation of acute decompensated
heart failure in adults", section on 'Clinical manifestations')

● Acute nephrotic syndrome (see "Overview of heavy proteinuria and the nephrotic
syndrome")

● Bilateral DVT, which is often associated with malignancy (see "Cancer-associated

hypercoagulable state: Causes and mechanisms")

Our approach to patients presenting with acute bilateral leg edema is as follows:

● Although much less likely than with acute unilateral leg edema, the possibility of DVT must
be considered. If the clinical probability of DVT is high (calculator 1 and calculator 2), we
proceed with CUS to evaluate for DVT. (See "Clinical presentation and diagnosis of the
nonpregnant adult with suspected deep vein thrombosis of the lower extremity", section
on 'Suspected first DVT (risk stratification)'.)

● If the clinical probability of DVT is low or moderate, we evaluate multiple possible

diagnoses simultaneously:

• We review the patient’s medication history and, if a drug known to cause edema has
been initiated or dose-escalated ( table 3), we discontinue it if possible. Spontaneous
resolution of the edema with discontinuation of the potentially offending agent makes
drug-induced edema likely.

• Patients presenting with dyspnea, orthopnea, paroxysmal nocturnal dyspnea,

tachypnea, tachycardia, rales, or distended neck veins should be evaluated for acute
heart failure. The approach to such patients is presented elsewhere. (See "Approach to
diagnosis and evaluation of acute decompensated heart failure in adults".)

• A semi-quantitative urine dipstick should be performed; if positive for protein, then a

quantitative urine protein-to-creatinine ratio and serum albumin should be measured.
(See "Overview of heavy proteinuria and the nephrotic syndrome".)

• A serum D-dimer should be measured. If elevated, a CUS is usually indicated to exclude

DVT. (See "Clinical presentation and diagnosis of the nonpregnant adult with suspected
deep vein thrombosis of the lower extremity", section on 'Suspected first DVT (risk
stratification)'.)

https://www.uptodate.com/contents/6878/print 7/27
3/30/23, 12:43 AM 6878

Chronic bilateral leg edema — Chronic venous disease is the most common cause of
chronic bilateral leg edema. However, chronic venous disease tends to be overdiagnosed in
such patients, whereas other important diagnostic considerations, including heart failure and
pulmonary hypertension (often related to sleep apnea), tend to be underdiagnosed. In one
study, for example, 32 of 45 patients presenting to a primary care practice with chronic bilateral
leg edema were initially diagnosed with chronic venous disease (71 percent), and 8 of 45
patients were diagnosed with heart failure (18 percent) [4]. After further evaluation, 15 had
heart failure and 19 had pulmonary hypertension as causes of bilateral edema (33 and 42
percent, respectively).

Less common causes of chronic bilateral leg edema include renal disease, liver disease, a pelvic
neoplasm, constrictive pericarditis, idiopathic edema, premenstrual edema, and malnutrition.
(See "Idiopathic edema".)

Lymphedema and myxedema are not true edematous states. Lymphedema can be primary
(usually presenting in childhood) or secondary. At the onset of lymphedema, it may be pitting,
but it becomes nonpitting over time as cutaneous fibrosis and adipose tissue deposition occurs.
(See "Clinical features and diagnosis of peripheral lymphedema".)

Myxedema is caused by the accumulation of glycosaminoglycans in the dermis. Pretibial

myxedema is nonpitting and can be a feature of autoimmune thyroid disease (most often
Graves’ disease), or may be present in severe hypothyroidism. Myxedema is discussed
elsewhere. (See "Pretibial myxedema (thyroid dermopathy) in autoimmune thyroid disease".)

Our approach to patients with chronic bilateral leg edema is as follows:

● The initial history and examination may be suggestive of a particular cause of chronic
bilateral leg edema. As examples:

• Patients with heart failure may present with chronic bilateral leg edema. In most cases,
patients have a known history of heart failure and will have associated symptoms and
signs such as dyspnea, orthopnea, and paroxysmal nocturnal dyspnea. Patients may
also note fatigue, anorexia, and abdominal distention. The examination findings in
heart failure are varied, but the most specific are extra heart sounds, hepatomegaly,
cardiomegaly, lung rales, and elevated jugular venous pressure. Evaluation of patients
with suspected heart failure is presented elsewhere. (See "Heart failure: Clinical
manifestations and diagnosis in adults", section on 'Clinical presentation'.)

• Chronic bilateral leg edema may be a manifestation of pulmonary hypertension caused

by conditions such as sleep apnea. Sleep apnea should be suspected if the patient has
https://www.uptodate.com/contents/6878/print 8/27
3/30/23, 12:43 AM 6878

excessive daytime sleepiness or is aware of loud snoring or interruptions of breathing

while sleeping. The evaluation of patients with suspected sleep apnea is discussed
separately. (See "Clinical presentation and diagnosis of obstructive sleep apnea in
adults".)

• Chronic bilateral leg edema can be a sign of advanced kidney or liver disease. Such
patients typically have other clinical features of the underlying disorder as well as
suggestive laboratory abnormalities. (See "Cirrhosis in adults: Etiologies, clinical
manifestations, and diagnosis", section on 'Clinical manifestations' and "Chronic kidney
disease (newly identified): Clinical presentation and diagnostic approach in adults".)

● If the initial history and examination do not suggest a particular cause of chronic bilateral
leg edema:

• We obtain a semi-quantitative urine dipstick for protein, serum creatinine, serum

albumin, prothrombin time, liver function tests, and thyroid-stimulating hormone.

• If these tests are suggestive of renal, liver, or thyroid disease, we pursue these
diagnoses. (See "Chronic kidney disease (newly identified): Clinical presentation and
diagnostic approach in adults" and "Cirrhosis in adults: Etiologies, clinical
manifestations, and diagnosis" and "Pretibial myxedema (thyroid dermopathy) in
autoimmune thyroid disease" and "Clinical manifestations of hypothyroidism", section
on 'Skin'.)

• By contrast, if these tests are unrevealing, we obtain an echocardiogram to evaluate

the possibility of heart failure or pulmonary hypertension. (See "Clinical features and
diagnosis of pulmonary hypertension of unclear etiology in adults", section on
'Echocardiography'.)

• If echocardiography is unrevealing, we assess the likelihood of chronic venous disease.

In such patients, the examination usually reveals skin findings, such as pigmentary
changes, induration, and ulceration ( picture 2). If these findings are present, we
make a presumptive diagnosis of chronic venous disease. (See "Clinical manifestations
of lower extremity chronic venous disease".)

• If typical skin findings of chronic venous disease are absent, we obtain imaging of the
pelvis to exclude a pelvic neoplasm or other lesion-causing venous outflow obstruction.
If ovarian cancer is suspected, we start with a transvaginal ultrasound; otherwise, we
obtain a contrast-enhanced CT scan of the pelvis.

https://www.uptodate.com/contents/6878/print 9/27
3/30/23, 12:43 AM 6878

Arm edema — Our approach to the differential diagnosis of arm edema in adults depends
upon the acuity of the edema.

Acute isolated upper extremity edema can be caused by trauma, infection, superficial
thrombophlebitis, or inflammatory arthritis of the upper extremity. In such cases, the
underlying etiology is typically apparent from the history and examination.

Upper extremity venous thrombosis should be suspected when none of the etiologies noted
above are present, or if there are other significant risk factors such as the presence of a venous
catheter. Spontaneous thrombosis occurs most often in muscular male athletes engaging in
strenuous activity with the involved arm and usually involves anatomic abnormalities of the
thoracic outlet. Acute bilateral upper extremity edema is rare but may be seen with bilateral
spontaneous venous thrombosis or superior vena cava syndrome. (See "Catheter-related upper
extremity venous thrombosis in adults" and "Primary (spontaneous) upper extremity deep vein
thrombosis" and "Malignancy-related superior vena cava syndrome".)

CUS with Doppler is the study of choice for the initial evaluation of patients with possible upper
extremity venous thrombosis. (See "Catheter-related upper extremity venous thrombosis in
adults", section on 'Diagnostic evaluation' and "Primary (spontaneous) upper extremity deep
vein thrombosis", section on 'Diagnosis'.)

More gradual swelling of the arm occurs with lymphedema. Lymphedema can be primary
(usually presenting in childhood) or secondary (usually following surgery or radiation
treatment). At the onset of lymphedema, it may be pitting, but it becomes nonpitting over time
as cutaneous fibrosis and adipose tissue deposition develop. (See "Clinical features and
diagnosis of peripheral lymphedema".)

Isolated pulmonary edema — Patients with pulmonary edema complain primarily of

shortness of breath and orthopnea. Physical examination usually reveals a tachypneic patient
with rales and possibly a diastolic gallop (S3). The diagnosis of pulmonary edema should be
confirmed by radiologic studies because other disorders, such as a pulmonary embolus, may
produce similar symptoms but will require different therapy ( image 1A-B). (See "Approach to
diagnosis and evaluation of acute decompensated heart failure in adults".)

Although cardiac disease (eg, acute myocardial infarction, heart failure, mitral or aortic valvular
pathologies) is the most common cause of pulmonary edema, it can also be produced by
volume overload due to primary renal sodium retention (such as acute glomerulonephritis) or
by increased capillary permeability in the acute respiratory distress syndrome. (See "Glomerular
disease: Evaluation and differential diagnosis in adults", section on 'Clinical manifestations of

https://www.uptodate.com/contents/6878/print 10/27
3/30/23, 12:43 AM 6878

glomerular disease' and "Acute respiratory distress syndrome: Clinical features, diagnosis, and
complications in adults".)

There are a number of other less common forms of noncardiogenic pulmonary edema,
including high-altitude pulmonary edema, neurogenic pulmonary edema, and pulmonary
edema related to opioid overdose. (See "Noncardiogenic pulmonary edema".)

In contrast to cardiac and renal disease, uncomplicated cirrhosis is not associated with
pulmonary edema. The intrahepatic sinusoidal obstruction in this disorder leads to selective
increases in venous and capillary pressures proximal to the hepatic vein [5]. The systemic
vascular resistance decreases in cirrhotic patients, and this generates relatively reduced blood
volume in the cardiopulmonary circulation [6]. (See "Hyponatremia in patients with cirrhosis".)

Pulmonary edema also does not occur due to isolated hypoalbuminemia [7]. Thus, in the
absence of a concurrent rise in left atrial and pulmonary capillary pressures, pulmonary edema
is not usually seen with hypoalbuminemia, even at a plasma albumin concentration low enough
to induce peripheral edema [8]. The reasons for this are presented elsewhere. (See
"Pathophysiology and etiology of edema in adults", section on 'Compensatory factors'.)

Ascites — Ascites is associated with abdominal distention and both shifting dullness and a fluid
wave on percussion of the abdomen. Causes of ascites include cirrhosis, hepatic veno-occlusive
disease (eg, Budd-Chiari syndrome), malignancy, and infection. Right-sided heart failure and
constrictive pericarditis can cause ascites, but these processes typically also cause peripheral
edema. If ascites is suspected, the diagnosis can be confirmed by ultrasonography. Abdominal
paracentesis is used to determine the cause of ascites. (See "Evaluation of adults with ascites".)

Other forms of edema

Lymphedema — The major causes of lymphedema in adults in developed countries are

axillary lymph node dissection in patients with breast cancer and axillary or inguinal lymph
node dissection in patients with melanoma. However, worldwide, the most common cause is
filariasis. The edema in such patients is typically limited to an arm or leg. The clinical hallmark of
lymphedema is the presence of cutaneous and subcutaneous thickening, as manifested by
cutaneous fibrosis, peau d'orange, and a positive Stemmer sign, which refers to an inability to
tent the skin at the base of the digits. (See "Clinical features and diagnosis of peripheral
lymphedema" and "Lymphatic filariasis: Epidemiology, clinical manifestations, and diagnosis",
section on 'Lymphedema'.)

Nonpitting edema — Pitting reflects movement of the excess interstitial water in response to
pressure. Testing for pitting involves applying firm pressure to the edematous tissue for at least
https://www.uptodate.com/contents/6878/print 11/27
3/30/23, 12:43 AM 6878

five seconds [1]. (See 'Peripheral edema' above.)

Nonpitting edema is primarily due to one of two disorders:

● Moderate to severe lymphedema, as can occur after radical mastectomy or with lymphatic
disease. However, pitting does occur in mild (stage I) and some cases of moderate (stage
II) lymphedema [9]. (See "Clinical features and diagnosis of peripheral lymphedema".)

● Pretibial myxedema, which occurs in patients with thyroid disease and is associated with
localized areas of swelling [5,6,10]. (See "Pretibial myxedema (thyroid dermopathy) in
autoimmune thyroid disease".)

Periorbital and scrotal edema — Periorbital and scrotal edema are localized forms of edema
that can be seen in systemic edematous states but should not be the sole manifestation of
edema in these disorders. The differential diagnosis of localized periorbital/facial edema and
acute idiopathic scrotal edema are discussed separately. (See "An overview of angioedema:
Clinical features, diagnosis, and management", section on 'Disorders resembling cutaneous
edema' and "Acute scrotal pain in adults", section on 'Other etiologies'.)

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Fluid and electrolyte
disorders in adults".)

INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the
Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade
reading level, and they answer the four or five key questions a patient might have about a given
condition. These articles are best for patients who want a general overview and who prefer
short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more
sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading
level and are best for patients who want in-depth information and are comfortable with some
medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print
or e-mail these topics to your patients. (You can also locate patient education articles on a

https://www.uptodate.com/contents/6878/print 12/27
3/30/23, 12:43 AM 6878

variety of subjects by searching on "patient info" and the keyword(s) of interest.)

● Basics topics (see "Patient education: Swelling (The Basics)")

● Beyond the Basics topics (see "Patient education: Edema (swelling) (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

● Pathophysiology – Edema is a palpable swelling produced by expansion of the interstitial

fluid volume. Generalized edema is produced by one or more of the following: increased
capillary hydrostatic pressure, decreased capillary oncotic pressure, and/or increased
capillary permeability ( table 1). The retention of sodium and water by the kidneys must
also occur for edema to develop. (See 'Overview of pathophysiology' above.)

● Evaluation of lower extremity edema – Our approach to the evaluation of leg edema in
adults depends upon whether the patient has unilateral/asymmetric edema or bilateral
edema, and upon the acuity of the edema. (See 'Leg edema' above.)

• Acute unilateral (or asymmetric) edema – In patients with acute unilateral or

asymmetric edema, we first evaluate for deep vein thrombosis (DVT). If DVT has been
excluded, we evaluate for other causes of acute unilateral or asymmetric edema
( table 2). (See 'Acute unilateral or asymmetric edema' above.)

• Chronic unilateral (or asymmetric) edema – In patients with chronic unilateral or

asymmetric edema, a diagnosis can generally be made based upon clinical features. If
the history and examination are not consistent with a particular diagnosis (eg, venous
insufficiency, lymphedema, or complex regional pain syndrome), we obtain
compression ultrasonography (CUS) with Doppler. If the CUS suggests pelvic outflow
obstruction, we obtain a transvaginal ultrasound or a contrast-enhanced computed
tomography (CT) scan of the pelvis. (See 'Chronic unilateral or asymmetric edema'
above.)

• Acute bilateral edema – In patients with acute bilateral leg edema, we first evaluate
for DVT. If DVT has been excluded, we assess for edema as a medication side effect
( table 3) or as a manifestation of acute heart failure or acute nephrotic syndrome
( table 2). (See 'Acute bilateral leg edema' above.)

• Chronic bilateral edema – In patients with chronic bilateral leg edema, a diagnosis
can often be made based upon clinical features ( table 2). If the history and
examination are not consistent with a particular diagnosis (eg, chronic venous disease,
https://www.uptodate.com/contents/6878/print 13/27
3/30/23, 12:43 AM 6878

heart failure, pulmonary hypertension, renal, or liver disease), we obtain a semi-

quantitative urine dipstick for protein and measure serum creatinine, serum albumin,
prothrombin time, liver function tests, and thyroid-stimulating hormone. If those tests
are unrevealing, we obtain an echocardiogram. If the echocardiogram does not
suggest the etiology of the edema, and chronic venous disease does not seem likely,
we obtain imaging of the pelvis to exclude venous outflow obstruction. (See 'Chronic
bilateral leg edema' above.)

● Evaluation of upper extremity edema – Our approach to the differential diagnosis of

arm edema in adults depends upon the acuity of the edema.

• Acute – Acute isolated upper extremity edema can be caused by trauma, infection,
superficial thrombophlebitis, or inflammatory arthritis of the upper extremity. Upper
extremity venous thrombosis should be suspected when none of the etiologies noted
above are present or if there are other significant risk factors such as the presence of a
venous catheter. CUS with Doppler is the study of choice for the initial evaluation of
patients with possible upper extremity venous thrombosis. (See 'Arm edema' above.)

• Subacute/chronic – More gradual swelling of the arm occurs with lymphedema. (See
'Arm edema' above.)

● Pulmonary edema – Patients with pulmonary edema complain primarily of shortness of

breath and orthopnea. Physical examination usually reveals a tachypneic patient with rales
and possibly a diastolic gallop (S3). The diagnosis of pulmonary edema should be
confirmed by radiologic studies because other disorders, such as a pulmonary embolus,
may produce similar symptoms but will require different therapy. (See 'Isolated pulmonary
edema' above.)

● Ascites – Ascites is associated with abdominal distention and both shifting dullness and a
fluid wave on percussion of the abdomen. If ascites is suspected, the diagnosis can be
confirmed by ultrasonography. (See 'Ascites' above.)

● Other presentations of edema – Other forms of edema include lymphedema,

myxedema, periorbital edema, and scrotal edema. (See 'Other forms of edema' above.)

Use of UpToDate is subject to the Terms of Use.

REFERENCES

https://www.uptodate.com/contents/6878/print 14/27
3/30/23, 12:43 AM 6878

1. Lawenda BD, Mondry TE, Johnstone PA. Lymphedema: a primer on the identification and
management of a chronic condition in oncologic treatment. CA Cancer J Clin 2009; 59:8.
2. Hull R, Hirsh J, Sackett DL, et al. Clinical validity of a negative venogram in patients with
clinically suspected venous thrombosis. Circulation 1981; 64:622.
3. Gorman WP, Davis KR, Donnelly R. ABC of arterial and venous disease. Swollen lower limb-
1: general assessment and deep vein thrombosis. BMJ 2000; 320:1453.
4. Blankfield RP, Finkelhor RS, Alexander JJ, et al. Etiology and diagnosis of bilateral leg edema
in primary care. Am J Med 1998; 105:192.

5. Guazzi M, Polese A, Magrini F, et al. Negative influences of ascites on the cardiac function
of cirrhotic patients. Am J Med 1975; 59:165.
6. Henriksen JH, Bendtsen F, Gerbes AL, et al. Estimated central blood volume in cirrhosis:
relationship to sympathetic nervous activity, beta-adrenergic blockade and atrial natriuretic
factor. Hepatology 1992; 16:1163.
7. Crandall ED, Staub NC, Goldberg HS, Effros RM. Recent developments in pulmonary edema.
Ann Intern Med 1983; 99:808.
8. Taylor AE, Parker JC. Pulmonary interstitial spaces and lymphatics. In: Handbook of Physiol
ogy. Section 3: The Respiratory System, Fishman AP, Fisher AB (Eds), American Physiological
Society, Madison, WI 1985. Vol I, p.167.
9. The diagnosis and treatment of peripheral lymphedema: 2003 consensus of the Internatio
nal Society of Lymphology Executive Committee www.u.arizona.edu/%7Ewitte/ISL.htm (Acc
essed on April 19, 2011).
10. Carrie BJ, Hilberman M, Schroeder JS, Myers BD. Albuminuria and the permselective
properties of the glomerulus in cardiac failure. Kidney Int 1980; 17:507.
Topic 6878 Version 33.0

https://www.uptodate.com/contents/6878/print 15/27
3/30/23, 12:43 AM 6878

GRAPHICS

Major causes of edema by primary mechanism

Increased capillary hydraulic pressure

Increased plasma volume due to renal sodium retention

Heart failure, including cor pulmonale

Primary renal sodium retention

Renal disease, including the nephrotic syndrome

Drugs:* Nonsteroidal antiinflammatory drugs (NSAIDs), glucocorticoids, fludrocortisone,

thiazolidinediones (glitazones), insulins, estrogens, progestins, androgens, testosterone,
aromatase inhibitors, tamoxifen; and by multiple mechanisms: vasodilators (hydralazine,
minoxidil, diazoxide) and calcium channel blockers (particularly dihydropyridines [ie,
amlodipine, nifedipine]); also refer to "Arteriolar vasodilation" below

Refeeding edema

Early hepatic cirrhosis

Pregnancy and premenstrual edema

Idiopathic edema, when diuretic induced

Sodium or fluid overload: Parenteral antibiotics or other drugs with large amounts of sodium,
sodium bicarbonate, or excessive or overly rapid fluid replacement

Venous obstruction or insufficiency

Cirrhosis or hepatic venous obstruction

Acute pulmonary edema

Local venous obstruction

Venous thrombosis

Venous stenosis

Chronic venous insufficiency – Post-thrombotic syndrome

Arteriolar vasodilation

Drugs:* Frequent – Vasodilators (hydralazine, minoxidil, diazoxide), dihydropyridine calcium

channel blockers; less frequent – alpha1 blockers, sympatholytics (ie, methyldopa),
nondihydropyridine calcium channel blockers [1]

Idiopathic edema

Hypoalbuminemia

https://www.uptodate.com/contents/6878/print 16/27
3/30/23, 12:43 AM 6878

Protein loss

Nephrotic syndrome

Protein-losing enteropathy

Reduced albumin synthesis

Liver disease

Malnutrition

Increased capillary permeability

Idiopathic edema

Burns

Trauma

Inflammation or sepsis

Allergic reactions, including certain forms of angioedema

Acute respiratory distress syndrome

Diabetes mellitus

Interleukin 2 therapy

Malignant ascites

Lymphatic obstruction or increased interstitial oncotic pressure

Lymph node dissection

Nodal enlargement due to malignancy

Hypothyroidism

Malignant ascites

Other drugs* (uncertain mechanism)

Anticonvulsant: Gabapentin, pregabalin

Antineoplastic: Docetaxel, cisplatin

Antiparkinson: Pramipexole, ropinirole

* Patients with decreased cardiac output, preexisting renal insufficiency, and/or receiving higher
doses are more likely to experience edema and edema-associated adverse events. This is not a
complete list of drugs associated with edema. For additional information, refer to the Lexicomp
individual drug monographs included with UpToDate.

Reference:
1. Messerli FH. Vasodilatory edema: A common side effect of antihypertensive therapy. Curr Cardiol Rep 2002; 4(6):479.

https://www.uptodate.com/contents/6878/print 17/27
3/30/23, 12:43 AM 6878

Graphic 53550 Version 13.0

https://www.uptodate.com/contents/6878/print 18/27
3/30/23, 12:43 AM 6878

Pitting edema

Reproduced with permission from: Bickley LS, Szilagyi PG. Bates' Guide to Physical
Examination and History Taking, 9th ed, Lippincott Williams & Wilkins, Philadelphia
2005. Copyright © 2005 Lippincott Williams & Wilkins.

Graphic 118097 Version 1.0

https://www.uptodate.com/contents/6878/print 19/27
3/30/23, 12:43 AM 6878

Major causes of bilateral lower extremity edema

Acute edema

Medications
Heart failure
Nephrotic syndrome
Venous thrombosis
Acute worsening of chronic causes

Chronic edema

Venous insufficiency
Heart failure
Left-sided with preserved or reduced ejection fraction
Right-sided
Pulmonary hypertension (including sleep apnea)
Restrictive pericarditis
Restrictive cardiomyopathy
Renal disease (including nephrotic syndrome)
Liver disease (early cirrhosis)
Premenstrual edema
Pregnancy
Malnutrition (including malabsorption and protein losing enteropathy)
Pelvic compression (including tumor or lymphoma)
Dependent edema
Sodium or fluid overload (including parenteral fluids, antibiotics and other drugs with large
amounts of sodium)
Refeeding edema
Idiopathic edema
Inflammation (including sepsis)
Medications

Chronic lymphedema

Primary lymphedema (presenting in childhood)

Secondary lymphedema (including lymph node dissection)
Thyroid disease (myxedema)

Graphic 118001 Version 1.0

https://www.uptodate.com/contents/6878/print 20/27
3/30/23, 12:43 AM 6878

Skin changes of chronic venous insufficiency

Longstanding edema in this patient with chronic venous

insufficiency led to moderately advanced pigment changes on the
medial and lateral ankles, which extend onto the dorsum of the foot.
The left medial ankle displays a healed venous ulcer below the
malleolus; the right lateral ankle has a small active venous ulcer
(arrow).

Courtesy of Patrick C Alguire, MD.

Graphic 56758 Version 3.0

https://www.uptodate.com/contents/6878/print 21/27
3/30/23, 12:43 AM 6878

Complex regional pain syndrome of the foot

Courtesy of: David D Sherry, MD.

Graphic 53380 Version 2.0

https://www.uptodate.com/contents/6878/print 22/27
3/30/23, 12:43 AM 6878

Medications associated with edema*

Common
Dihydropyridine calcium channel blockers

Amlodipine
Felodipine
Isradipine
Nicardipine
Nifedipine
Nimodipine
Nitrendipine

Other vasodilators

Hydralazine
Minoxidil
Alpha-blockers

Endocrine

Thiazolidinediones
Rosiglitazone
Pioglitazone
Glucocorticoids
Fludrocortisone
Estrogen
Progesterone
Tamoxifen
Aromatase inhibitors
Testosterone
Androgens

Less common

Nondihydropyridine calcium channel blockers

Verapamil
Diltiazem

Anticonvulsant

Gabapentin
Pregabalin

Antineoplastic

https://www.uptodate.com/contents/6878/print 23/27
3/30/23, 12:43 AM 6878

Docetaxel
Cisplatin
Interleukin 2 therapy

Antiparkinson

Pramipexole
Ropinirole

Antidepressants

Monoamine oxidase inhibitors

Trazodone

Other

Diazoxide
NSAIDs
Proton pump inhibitors

NSAIDs: nonsteroidal antiinflammatory drugs.

* This is not a complete list of drugs associated with edema. For additional information, refer to the
Lexicomp individual drug monographs included with UpToDate.

Graphic 118003 Version 2.0

https://www.uptodate.com/contents/6878/print 24/27
3/30/23, 12:43 AM 6878

Radiograph and CT of acute pulmonary edema

(A) An anteroposterior radiograph shows perihilar consolidations and air bronchograms (arrows) of acute
alveolar edema.

(B) A coronal reconstruction of a CT scan of the same patient shows acute alveolar edema with diffuse
perihilar infiltrates and air bronchograms (arrows).

CT: computed tomography.

Graphic 98495 Version 3.0

https://www.uptodate.com/contents/6878/print 25/27
3/30/23, 12:43 AM 6878

Hydrostatic pulmonary edema

Pulmonary edema in a "butterfly distribution" due to left ventricular

failure. Chest radiograph shows large perihilar opacities in patient
with enlarged cardiac silhouette.

Courtesy of Paul Stark, MD.

Graphic 58394 Version 5.0

https://www.uptodate.com/contents/6878/print 26/27
3/30/23, 12:43 AM 6878

Contributor Disclosures
C Christopher Smith, MD No relevant financial relationship(s) with ineligible companies to
disclose. Mark D Aronson, MD No relevant financial relationship(s) with ineligible companies to
disclose. Michael Emmett, MD No relevant financial relationship(s) with ineligible companies to
disclose. Jane Givens, MD, MSCE No relevant financial relationship(s) with ineligible companies to
disclose.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must
conform to UpToDate standards of evidence.

Conflict of interest policy

https://www.uptodate.com/contents/6878/print 27/27