Differentials
Common
Heart failure with reduced ejection fraction (HFrEF)
History
dyspnea, orthopnea, and paroxysmal nocturnal dyspnea, angina
Exam
bilateral edema, S3 gallop, rales, cool extremities, hepatomegaly, ascites, elevated jugular venous pressure
1st investigation
Heart failure with preserved ejection fraction (HFpEF)
History
more likely in patients who are female, of advanced age, and possibly those with history of hypertension; dyspnea, orthopnea, and paroxysmal nocturnal dyspnea
Exam
bilateral edema; no examination feature clearly distinguishes systolic from diastolic heart failure; S4, rales, hepatomegaly, or ascites may be found; elevated jugular venous pressure
1st investigation
Cor pulmonale
History
history of COPD, pulmonary emboli, or sleep apnea may suggest pulmonary hypertension resulting in cor pulmonale
Exam
bilateral edema; abnormal lung examination with wheezing or rales; ascites and hepatomegaly; elevated jugular venous pressure
1st investigation
- echocardiography:
elevated pulmonary arterial pressure
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Other investigations
- spirometry:
reduced forced expiratory volume in one second (FEV1) with a reduced absolute FEV1/forced vital capacity (FVC) ratio suggests an obstructive pattern; reduced FEV1 with a normal or increased absolute FEV1/FVC ratio suggests a restrictive pattern
- CT scan of chest:
hyperexpansion and bulla of emphysema or segmental filling defects of pulmonary emboli
- V/Q scan:
segmental filling defects of pulmonary emboli
- polysomnography:
hypopnea/apnea episodes
- right heart catheterization:
elevated right heart pressure
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Sleep apnea
History
snoring, respiratory pauses during sleep; daytime somnolence
Exam
bilateral edema; obesity, large tonsils, short neck with large circumference
1st investigation
- echocardiography:
pulmonary hypertension
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Other investigations
- polysomnography:
hypopnea/apnea episodes
Deep vein thrombosis
History
acute/subacute calf pain and unilateral edema; pain may be localized over the deep venous system; risk factors include immobility, malignancy, personal, or family history of prior thromboembolic disease, surgery, pregnancy, or hormonal therapy; the Wells clinical prediction rule predicts pretest probability
Exam
unilateral edema; asymmetric tenderness, warmth, erythema, and palpable cords behind the leg; dilated superficial veins over the foot and leg; normal jugular venous pressure
1st investigation
Other investigations
- venography:
positive when thrombus is found
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Chronic venous insufficiency
History
chronic swelling, aching, heavy sensation of the legs, worse after standing; risk factors include older age, female sex, obesity, pregnancy, family history of varicose veins, prior leg injury, or history of venous thrombosis
Exam
bilateral or unilateral leg edema; dark reddish-brown skin hyperpigmentation over the shins or skin ulcerations around malleoli; varicose veins; eczematous changes (venous dermatitis); lipodermatosclerosis creating inverted bottle-like contour; white scars/atrophic blanche; normal jugular venous pressure
1st investigation
- none:
no initial test, diagnosis is usually clinical
Other investigations
- duplex ultrasound:
may show location of venous incompetence and degree of venous reflux
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Nephrotic syndrome
History
frothing of urine from increased protein content; change in urine frequency or color may be seen
Exam
bilateral and generalized edema from hypoproteinemia; edema may be seen in the periorbital region as well as in the extremities; normal jugular venous pressure
1st investigation
Other investigations
- urine microscopy:
fat droplets inside kidney cells shed into the urine (oval fat bodies), which appear like a cross under polarized light (Maltese cross)
- spot urine protein:
protein-creatinine ratio >0.3 g protein per 1 mmol creatinine
- 24-hour urine collection:
>3.5 g/dL (proteinuria)
Cirrhosis
History
risk factors for viral hepatitis, excess alcohol consumption, Wilson disease, hemochromatosis, primary sclerosing cholangitis, primary biliary cirrhosis, autoimmune hepatitis, metabolic dysfunction-associated steatohepatitis (formerly known as nonalcoholic steatohepatitis), alpha-1-antitrypsin deficiency; some cases are cryptogenic; may have constitutional symptoms e.g. fatigue, weakness and weight loss
Exam
bilateral edema; liver shrunken and nodular; splenomegaly and/or ascites; jaundice and scleral icterus; engorged periumbilical veins (caput medusae); spider nevi; normal jugular venous pressure
1st investigation
- liver function tests (including coagulation studies):
low albumin, prolonged prothrombin time, and increased bilirubin suggests liver synthetic and metabolic dysfunction
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Other investigations
- liver ultrasonography with duplex:
small scarred liver with elevated portal pressure and splenomegaly
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Pregnancy
History
pregnancy is commonly associated with lower-extremity edema starting in the second trimester, due to increased total body fluid as a result of hormonal changes and mechanical pressure on the inferior vena cava from the gravid uterus
Exam
bilateral edema, usually mild; pregnancy should be clinically evident by the time it begins to cause peripheral edema
1st investigation
- human chorionic gonadotropin:
positive
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Other investigations
Medication-induced edema
History
onset of edema coincides with initiation of medication; use of calcium-channel blocking agents (especially dihydropyridines), agents that cause vasodilation (minoxidil, diazoxide), or agents that block renal prostaglandin synthesis (nonsteroidal anti-inflammatory drugs) causes renal fluid and salt retention and contributes to peripheral edema; other medication classes associated with peripheral edema include antidepressants, estrogens, corticosteroids, intrathecal opioids, gabapentin or pregabalin, mitogen-activated protein kinase enzyme inhibitors, hypoglycemic agents in the thiazolidinedione class and levodopa.
Exam
bilateral edema; normal jugular venous pressure
1st investigation
- none:
no specific tests; clinical suspicion is driven by new medication use prior to onset of edema and supported by improvement in edema with medication withdrawal
Other investigations
Premenstrual edema
History
onset of edema is related to the hormone fluctuations that occur during the normal menstrual cycle; appears in a cyclic pattern, most often in the luteal phase (the 5-7 day window prior to menses); may be a symptom experienced as a part of premenstrual syndrome, and therefore may be associated with other symptoms such as sadness, irritability, fatigue, or breast tenderness or swelling; secondary to hormone normalization
Exam
may reveal a cyclical pattern of weight gain and lower extremity edema during the luteal phase (the 5-7 day window prior to menses)
1st investigation
- none:
no initial test; diagnosis is usually clinical
Other investigations
Uncommon
Pericardial effusion
History
substernal chest pain, dyspnea, and dizziness; history of risk factors for pericardial effusion (connective tissue disease, chest trauma, myocardial infarction, cardiac surgery, uremia, tuberculosis, or malignancy)
Exam
bilateral edema; pulsus paradoxus; severe cases may have hypotension; loss of jugular atrial Y descent; muffled heart sounds; potential pericardial rub; elevated jugular venous pressure
1st investigation
Other investigations
Constrictive pericarditis
History
risk factors (radiation exposure, connective tissue disease, chest trauma, myocardial infarction, cardiac surgery, uremia, tuberculosis, or malignancy); history of pericarditis; gradual development of symptoms of cardiac congestion
Exam
bilateral edema, ascites, hepatomegaly; pericardial knock; large Y descent of jugular pressure, Kussmaul sign (rise in jugular venous pressure on inspiration); elevated jugular venous pressure
1st investigation
Other investigations
Restrictive cardiomyopathy
History
history of infiltrative disease such as amyloidosis or hemochromatosis
Exam
bilateral edema, hepatomegaly, ascites, Kussmaul sign (rise in jugular venous pressure on inspiration), S3, mitral regurgitation murmur, elevated jugular venous pressure
1st investigation
Other investigations
Tricuspid regurgitation
History
history of congenital valve defects, rheumatic heart disease, or endocarditis
Exam
bilateral edema; holosystolic murmur at left lower sternal border; prominent ventricular impulse in the left parasternal region; hepatomegaly; elevated jugular venous pressure
1st investigation
- echocardiography:
tricuspid valvular regurgitation
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Other investigations
Nonthrombotic venous outflow obstruction
History
unilateral leg pain and swelling (affects the left leg only in May-Thurner syndrome [compression of the left common iliac vein by the overlying right common iliac artery]); increases risk for deep vein thrombosis in the affected vein; may be history of prior thrombus
Exam
unilateral leg edema (affecting left leg only in May-Thurner syndrome); potentially cutaneous signs of chronic venous insufficiency; normal jugular venous pressure
1st investigation
Other investigations
- venography:
positive when venous stenosis is observed
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Hepatic venous outflow obstruction (includes Budd-Chiari syndrome and hepatic veno-occlusive disease)
History
right upper quadrant abdominal pain; thrombophilia and/or hematologic disorders such as myeloproliferative disorders or paroxysmal nocturnal hemoglobinuria; prior stem cell transplant, liver irradiation, or chemotherapy increases risk of hepatic veno-occlusive disease
Exam
bilateral edema; tender hepatomegaly, jaundice, ascites
1st investigation
Other investigations
Renal failure
History
decreased urinary output; hematuria
Exam
bilateral edema; may have associated ascites or pulmonary rales; hypertension may be seen; elevated jugular venous pressure from total body fluid overload
1st investigation
Other investigations
Protein-losing enteropathy
History
severe diarrhea suggests protein-losing enteropathy
Exam
bilateral edema from hypoproteinemia is generalized and may be seen in the periorbital region as well as in the extremities; normal jugular venous pressure
1st investigation
- serum albumin:
albumin level <2 g/dL is usually required to cause peripheral edema
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Other investigations
Angioedema
History
family history of angioedema or recent exposure to a medication such as an ACE inhibitor may be elicited
Exam
edema is diffuse in anaphylaxis but may be localized in angioedema or focal infection; normal jugular venous pressure
1st investigation
- none:
there are no specific tests, suspicion is usually driven by clinical features
Sepsis
History
symptoms of localized infection, nonspecific symptoms include fever or shivering, dizziness, nausea and vomiting, muscle pain, feeling confused or disoriented; may be history of risk factors e.g., immunosuppression, pregnancy or postpartum period, frailty, recent surgery or invasive procedures, intravenous drug use, or breach of skin integrity
Exam
bilateral edema; diffuse, develops after fluid resuscitation; tachycardia, tachypnea, hypotension, fever (>100.4ºF [>38ºC]) or hypothermia (<96.8ºF [<36ºC]), prolonged capillary refill, mottled or ashen skin, cyanosis, low oxygen saturation, newly altered mental state, reduced urine output
1st investigation
- blood culture:
may be positive for organism
More - serum lactate:
may be elevated; levels >18 mg/dL (>2 mmol/L) associated with adverse prognosis; even worse prognosis with levels ≥36 mg/dL (≥4 mmol/L)
More - CBC with differential:
WBC count >12×10⁹/L (12,000/microliter) (leukocytosis); WBC count <4×10⁹/L (4000/microliter) (leukopenia); or a normal WBC count with >10% immature forms; low platelets
More - C-reactive protein:
elevated
- BUN and serum electrolytes:
serum electrolytes may be deranged; blood urea may be elevated
- serum creatinine:
may be elevated
More - liver function tests:
may show elevated bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma glutamyl transpeptidase
More - coagulation studies:
may be abnormal
- ABG:
may be hypoxia, hypercapnia, elevated anion gap, metabolic acidosis
Other investigations
- ECG:
may show evidence of ischemia, atrial fibrillation, or other arrhythmia; may be normal
More - CXR:
may show consolidation; demonstrates position of central venous catheter and tracheal tube
- urine microscopy and culture:
may be positive for nitrites, protein or blood; elevated leukocyte count; positive culture for organism
- sputum culture:
may be positive for organism
- lumbar puncture:
may be elevated WBC count, presence of organism on microscopy and positive culture
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Compartment syndrome
History
trauma, fracture, or infection in the extremities
Exam
unilateral edema; pain in extremity may be severe, especially on passive stretch of the muscle; compartment tense to palpation; muscle weakness; hypoesthesia; normal jugular venous pressure; pulses and capillary refill may be normal
1st investigation
- compartment pressure testing:
variable; differential pressure within 20-30 mmHg of the diastolic pressure (delta pressure) is considered a strong indicator for fasciotomy
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Other investigations
- computed tomography:
evidence of the mechanism of the injury (e.g., fracture, bleeding)
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Primary lymphedema
History
can result from congenital lymphedema, lymphedema praecox, lymphedema tarda, yellow nail syndrome, or Turner syndrome; family history of similar symptoms supports diagnosis of congenital lymphedema
Exam
unilateral or bilateral edema; initially pitting; chronic edema causes fibrosis, hyperkeratosis, rough skin texture, and nonpitting edema; Stemmer sign is indicative (i.e., inability to pinch and lift a fold of skin at the base of the second toe); jugular venous pressure normal; lymphedema graded on a 3-stage scale
1st investigation
- none:
no initial test, diagnosis is usually clinical
Other investigations
- lymphoscintigraphy:
normal result shows symmetrical transport of the tracer through discrete lymph nodes; slow movement of tracer suggests hypoplasia of the lymphatic system; tracer outside of lymph routes suggests obstruction
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Secondary lymphedema
History
secondary lymphedema caused by malignancy, prior radiation, surgery, or infection (e.g., filariasis); history focuses on these possibilities and eliciting systemic symptoms such as unexplained weight loss
Exam
unilateral or bilateral, initially pitting; if chronic, causes fibrosis, hyperkeratosis, rough skin texture, and nonpitting edema; unilateral lymphedema following cancer treatment may be measured as the circumference of the affected limb being >2 cm or volume >10% compared with the unaffected limb; Stemmer sign is indicative (i.e., inability to pinch and lift a fold of skin at the base of the second toe); normal jugular venous pressure
1st investigation
- none:
no initial test, diagnosis is usually clinical
Other investigations
- lymphoscintigraphy:
normal result shows symmetric transport of the tracer through discrete lymph nodes; slow movement of tracer suggests hypoplasia of the lymphatic system; tracer outside of lymph routes suggests obstruction
More - Giemsa stain of peripheral blood smear:
microfilaria of Wuchereria bancrofti or Brugia spp. present in filariasis
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Idiopathic
History
onset age 20 to 60 years, usually in the third or fourth decade; worsened by orthostatic position; cyclical pattern but not associated with menses; may be associated with psychological symptoms and diuretic, laxative, or bulimic behaviors
Exam
bilateral edema periodic swelling of extremities and face; abdominal bloating; normal jugular venous pressure
1st investigation
- none:
no routine tests, as this is a diagnosis of exclusion
Other investigations
Severe malnutrition
History
longstanding and profound decreased dietary intake
Exam
bilateral edema from hypoproteinemia is generalized and may be seen in the periorbital region as well as in the extremities; muscle wasting from malnutrition should be evident, although muscle loss induced by protein deficiency may be masked by fluid retention; normal jugular venous pressure
1st investigation
- serum albumin:
albumin level of <2 g/dL is usually required to cause peripheral edema
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Other investigations
Hypothyroidism/myxedema
History
fatigue, cold intolerance, dry skin, constipation, weight gain, coarse hair
Exam
bilateral nonpitting edema occurs on the backs of the hands, and in periorbital and pretibial regions; normal jugular venous pressure
1st investigation
- thyroid-stimulating hormone (TSH):
elevation of TSH suggests hypothyroidism
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Other investigations
Ruptured popliteal fossa cyst
History
acute, unilateral, painful calf swelling; symptoms may be clinically similar to deep vein thrombosis; gastrocnemius bursa cysts are more common in knees with prior pathology such as arthritis
Exam
unilateral edema; may have been a palpable enlargement of the gastrocnemius bursa prior to rupture; normal jugular venous pressure
1st investigation
- ultrasound:
hypoechoic regions superficial to the muscles of the mid calf
Other investigations
Pelvic tumor causing external pressure on pelvic veins
History
back pain, hematuria, flank pain, abdominal bloating, abnormal vaginal bleeding or discharge, or unintentional weight loss
Exam
a mass may be felt upon palpation of the abdomen
1st investigation
- ultrasound of abdomen:
transvaginal is most common; may reveal complex components, bilateral tumors, ascites, mass >10 cm, and mural nodules
More - computed tomography scan of abdomen:
recommended as a first test in men and a second test (after transvaginal ultrasound) in women; may reveal presence of pelvic mass
Other investigations
- MRI of abdomen:
may reveal presence of pelvic mass
- PET scan:
may be useful once mass has been detected, to differentiate between malignant and benign pelvic mass, as well as assess for metastases
- cystoscopy:
may be used for evaluation of hematuria; may reveal lesions or mass that can be biopsied and resected during the procedure
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