Lower Extremity Edema Case File

Lower Extremity Edema Case File

Eugene C. Toy MD, Donald Briscoe, MD, FA  AFP, Bruce Britton, MD, Joel J. Heidelbaugh, MD, FA  AFP, FACG

Case 60

A 52-year-old healthy man presents to your office complaining of a 2-year history of bilateral leg swelling and intermittent heaviness that has become more bothersome over the past 3 months. He works as a mailman and states that this heaviness is increasingly impairing his ability to complete his route. He tells you "The swelling in my legs is often worse in the evening, especially when I have been walking all day:' By the end of the day, he has swelling up to his mid-calves and that the top of his socks leave deep indentations in his skin. He complains of brown spots and dryness and itching on his feet and ankles. He denies unusual shortness of breath, fatigue, sleep disturbance, but states that he has been using over-the-counter (OTC) ibuprofen for several months for knee pain. On examination, his body mass index (BMI) is 23 kg/m2, blood pressure is 130/85 mm Hg, pulse is 72 beats/min, and respiratory rate is 16 breaths/min. His heart, lung, and abdominal examinations are unremarkable. On examination of his extremities, he has symmetrical bilateral edema to his mid-calves with pitting, prominent varicose veins, and brown 2-mm sized macules on his feet and ankles. His posterior tibialis and dorsalis pedis pulses are 2+ bilaterally and his feet are warm.

⯈ What is the most likely diagnosis?

⯈ What further evaluation should be considered?

⯈ What is the initial step in therapy?

ANSWER TO CASE 60:

Lower Extremity Edema

Summary: A 52-year-old man presents with classic signs and symptoms of peripheral venous insufficiency. It is bilateral, chronic, and dependent and without significant constitutional, cardiac, or pulmonary symptoms. Physical examination reveals varicosities and venous stasis dermatitis. The edema often interferes with and is aggravated by his work and is possibly worsened with the recent use of ibuprofen.

• Most likely diagnosis: Venous insufficiency and varicose veins, aggravated by use of nonsteroidal anti-inflammatory drugs (NSAIDs).
• Further evaluation necessary: Ensure that there are no comorbid conditions: sleep studies and echocardiography if obstructive sleep apnea (OSA) and pulmonary hypertension are considered; echocardiogram, chest radiograph (CXR), electrocardiogram (ECG), brain natriuretic peptide (BNP) if congestive heart failure (CHF) or other cardiac cause is considered; serum electrolytes, serum creatinine, and urinalysis if renal causes are considered; serum albumin if low-protein or malabsorption states are considered. Ankle brachia! index (ABI) testing should be considered if potential treatments could aggravate peripheral arterial disease (PAD).
• Beneficial treatment: Leg elevation, compression stockings, low-sodium diet, and avoidance of medications that may cause edema. Consider oral horse chestnut seed extract for edema. Surgical options should be considered if comorbid PAD or venous stasis ulcers are present. Appropriate antibiotic and wound care therapy should be instituted when skin disruption is present to treat infection and maximize wound healing.

ANALYSIS

Objectives

1. Become familiar with the presenting signs and symptoms of common causes of lower extremity swelling.
2. Understand the clinical evaluation used to diagnose and identify low-risk lower extremity swelling from swelling indicative of severe comorbid conditions or those causes with significant risk.
3. Become familiar with the management of common causes of lower extremity swelling.
4. Define different types of lower extremity swelling and levels of lower extremity edema.

Considerations

In older people, chronic venous insufficiency is the most common cause of bilateral lower extremity swelling, affecting up to 2% of the general population, with increasing prevalence with age and obesity. Although venous insufficiency can often be diagnosed clinically without extensive testing, for persons older than 45 years there is an increased risk of pulmonary hypertension (most commonly secondary to obstructive sleep apnea) and congestive heart failure as the etiology of the lower extremity swelling. There are many medications also associated with fluid retention and should always be considered in the differential as a potential cause of or contributor to lower extremity swelling.

Approach To:

Lower Extremity Edema

DEFINITIONS

VENOUS EDEMA: An excess of low viscosity, protein-poor interstitial fluid resulting in pitting in the affected area of the body.

LYMPHEDEMA: An excess of protein-rich interstitial fluid within the skin and subcutaneous tissue. Primary forms are rare and often genetically related. Secondary lymphedema is more common and often related to previous malignancies, surgery, radiation, and infections.

LIPIDEMA: A form of fat maldistribution that can appear to be leg swelling with foot sparing, and is not a true form of edema.

MYXEDEMA: A dermal edema secondary to an increased deposition of connective tissue components (mucopolysaccharides) seen in various forms of thyroid disease.

CLINICAL APPROACH

Edema is defined as a visible and palpable swelling comprised of interstitial fluid. The most common cause of leg edema in North American patients older than 50 years is venous insufficiency, as it affects up to 30% of the population. CHF affects around 1 % of adults. The mostly likely cause of leg edema in women younger than 50 years is idiopathic edema, and may be confused with obesity. Most patients should be assumed to have one of these causes unless a history and physical indicate an underlying secondary cause. The two exceptions to this rule are in cases of pulmonary hypertension and undiagnosed CHF. These conditions may present with lower extremity edema prior to formal diagnosis.

DIAGNOSIS

History

The key elements of the history in evaluating the patient with lower extremity edema include the duration of edema (acute [<72 hours], vs chronic), presence of pain, current medications, overnight improvement when sleeping (indicating dependent edema), signs or symptoms of OSA ( eg, snoring, daytime somnolence), and history of chronic medical conditions including heart, liver, and kidney disease, or past history of pelvic or abdominal malignancies or radiation therapy. Family history of clotting disorders, varicosities, and lymphedema are also important to document.

Physical Examination

The key elements of the physical examination in the patient with lower extremity edema include signs of OSA including a body mass index (BMI) greater than 30 kg/m2 and a thick neck circumference greater than 17 in (42 cm). Unilateral leg swelling is commonly seen with venous insufficiency, lymphedema, and deep vein thrombosis (DVT ). Bilateral leg swelling is commonly seen with bilateral venous insufficiency, medication side effects, and idiopathic or systemic causes. Generalized edema is seen in advanced systemic diseases including CHF, renal failure, and liver failure. Tenderness of the swelling can be seen with DVTs and lipedema. Pitting is commonly encountered with venous edema, DVT, CHF, and early lymphedema; myxedema and chronic lymphedema do not cause pitting. Varicose veins are common in patients with chronic lymphedema, and a Kaposi-Stemmer sign (inability to pinch a fold of skin on dorsum of foot at base of second toe) is seen.

Common skin changes in lower extremity edema include hemosiderin deposition (brown pigmented spots), dry dermatitis, and skin ulceration (in cases of venous insufficiency), warm, tender, moist skin (as in complex regional pain syndrome), brawny induration, and warty texture with papillomatosis (lymphedema). Signs of underlying systemic disease include jaundice, ascites, and spider hemangioma (in liver disease and cirrhosis) and jugular venous distention, hepatojugular reflex, and rales on pulmonary examination (in congestive heart failure).

Diagnostic Studies

The majority of patients older than 50 years who present with leg swelling have venous insufficiency. Pulmonary hypertension (due to OSA or other causes) should always be in the differential of likely venous insufficiency. If the etiology is unclear, a complete blood count (CBC), comprehensive metabolic profile, urinalysis, and thyroid-stimulating hormone (TSH) can potentially rule out common systemic diseases associated with leg swelling. Proteinuria and serum albumin less than 2 g/dL are diagnostic for nephrotic syndrome. If the patient is found to have nephrotic syndrome, a fasting serum lipid profile should also be obtained.

If the clinical history and examination indicate a cardiac etiology, obtaining an electrocardiogram, echocardiogram, BNP, and chest radiograph should be obtained. A normal BNP can rule out CHF with a sensitivity of 90%.

In young women with idiopathic lower extremity edema who desire testing confirmation, or if the etiology is unclear, a morning to evening weight gain of greater than 0.7 kg may confirm the diagnosis. A water load test can be performed by drinking 20 cc/kg (max 1500 cc) in the morning and collecting all urine 1 hour prior to consumption until 4 hours after, then repeating. In the first trial, the patient must stand for the 4-hour time frame. In the second trial, the patient must remain recumbent. In cases of idiopathic edema, less than 55% of water consumed will be voided in the standing position and greater than 65% will be voided in recumbent position. Idiopathic edema is often associated with obesity and with depression.

Patients may complain of hand and face swelling in addition to leg swelling. On history, many patients may be taking diuretics to self-treat, or may be present asking for "water pills" to decrease the edema.

If a DVT is suspected (as in cases of acute edema), a D-dimer level should be obtained. Due to its high sensitivity yet low specificity, a normal n-dimer level essentially rules out a DVT, yet a positive n-dimer is not diagnostic of DVT. If the D-dimer is positive, then a venous Doppler ultrasonography of the lower extremities should be obtained. In patients with intermediate-to-high pretest probability of DVT, negative ultrasonography alone is insufficient to exclude the diagnosis of DVT. Further assessment is recommended, including repeating ultrasonography in 1 week if the D-dimer is elevated. An echocardiogram should be considered in patients greater than 45 years to rule out pulmonary hypertension or in any patient in whom OSA is suspected, and a polysomnogram should be obtained to evaluate this condition. If liver disease is suspected, then liver function tests and coagulation studies should be obtained. If a malignancy is suspected, then an abdominal and pelvic examination and computed tomography (CT) scan should be considered. Tumors commonly associated with lower extremity edema include prostate cancer, ovarian cancer, and lymphoma.

TREATMENT

Idiopathic Edema

Lifestyle modifications necessary to manage idiopathic edema include intermittent recumbency or leg elevation, avoidance of heat, low-sodium diet, decreased fluid intake, and weight loss. Patients with this disorder often have a secondary hyperaldosteronism due to this condition. Therefore, spironolactone dosed in the early evening has proven benefit in volume reduction. If not successful, a thiazide diuretic can be added as well. Loop diuretics should be avoided due to a higher risk of electrolyte abnormalities (eg, hypokalemia) and renal insufficiency. Compression stockings are less successful with this condition. Diuretic abuse is common among patients with idiopathic edema, and can lead to a mild hypovolemia that can stimulate renin-angiotensin-aldosterone secretion, which can lead to rebound edema when the diuretic is stopped. Diuretic-induced rebound edema can be minimized by weaning off the diuretic over a 3- to 4-week period. Patients need to be reassured that the initial worsening of edema is common with the withdrawal of diuretics but should normalize.

Venous Insufficiency

For patients with venous insufficiency, nonpharmacologic therapies include compression leg stockings and leg elevation. Often higher compressions of 30 to 40 mm Hg at the ankle are required to adequately control the swelling. If arterial insufficiency is a consideration, then venous and arterial Doppler ultrasonography should be performed prior to application of the stockings. Higher compression stockings can be difficult for some patients to put on, so patients should be instructed to put them on upon awakening before the leg swelling progresses. Advising the patient to roll the stockings off at the end of the day so that they can be rolled back on in the morning is also helpful. Stocking applicators can also be prescribed.

Horse chestnut seed extract inhibits elastin and hyaluronidase which in a 300-mg twice-daily dosing has been shown to modestly decrease symptoms associated with venous insufficiency. Loop diuretics in low doses can be used short term for patients who are severely affected. Surgical interventions are available for patients with severe disease who are unresponsive to less-invasive measures.

Lymphedema

Patients with lymphedema should be educated regarding the chronic nature of the condition. Reasonable expectations for treatment must be set and understood, as this condition is often difficult to manage. Treatments include exercise, elevation, intermittent pneumatic compression devices, manual lymph drainage massage, and surgical procedures. Diuretics are typically not helpful, but may be commonly used for comorbid conditions that contribute to volume overload including CHF and liver failure. Patients with chronic lymphedema are at a great risk of development of cellulitis. For patients with recurrent cellulitis, prophylactic antibiotics should be considered.

Deep Vein Thrombosis

Acute DVT requires prompt treatment with commencement of anticoagulation. Treatment options include low-molecular-weight heparin (eg, enoxaparin), warfarin, and direct Xa inhibitors (eg, rivaroxaban). The therapeutic goal for warfarin therapy should be a target international normalized ratio (INR) of 2.0 to 3.0. The duration of anticoagulation therapy varies based on cause and recurrence rate of the DVT. In initial cases of uncomplicated DVT, 3 months of anticoagulation is warranted. In cases of recurrent DVT and/or concomitant pulmonary embolism, then long-term anticoagulation is the standard of care. If anticoagulation therapy is contraindicated, then inferior vena cava (IVC) filter placement may be indicated to prevent life-threatening pulmonary embolism.

CASE CORRELATION

• See also Case 27 (Congestive Heart Failure).

COMPREHENSION QUESTIONS

60.1 A 60-year-old woman presents for follow-up of lymphedema that developed following a mastectomy and lymph node dissection for breast cancer. She finds the swelling to be very uncomfortable and limits the use of her right arm. Which of the following treatment options are recommended?

A. Intermittent pneumatic compression

B. Oral warfarin

C. Oral furosemide

D. Oral hydrochlorothiazide

E. Horse chestnut seed extract

60.2 Which patient would have the most benefit from a laboratory or diagnostic testing evaluation for systemic disease as a cause of lower extremity swelling?

A. A 35-year-old woman with cyclic bilateral ankle swelling without significant pain. She is taking OTC ibuprofen for her menstrual cramps. On examination, she has + 1 pitting at the ankles.

B. A 44-year-old man with a 3-year history of left greater than right, pain free, moderate swelling in his calves. He has a normal BMI, no daytime somnolence, and no constitutional symptoms. He is not taking any OTC or prescription medications. On examination, he has mild varicosities and hemosiderin skin deposits on both legs with non tender + 1 pitting edema. Calf circumferences measure 17 cm on the left and 15.5 cm on the right.

C. A 50-year-old man with +2 bilateral lower extremity edema that has slowly been worsening over the last year. He has a history of hypertension and is taking hydrochlorothiazide, benazepril, and amlodipine. On review of systems, he complains of daily fatigue, and some increasing constipation.

D. A 25-year-old woman on oral contraceptives with bilateral +1 lower extremity pitting swelling over a 2-year period. On examination, she has a body mass index of 26 kg/m2, no varicosities, no skin changes, and an otherwise negative review of symptoms. She does admit to using OTC weight-loss aids regularly.

60.3 A 65-year-old man with a history of prostate cancer and radiation therapy 3 years ago presents with chronic bilateral leg swelling. He denies dyspnea, chest pain, orthopnea, or wheezing. He denies daytime somnolence or snoring. On examination, he has nonpitting up to his calves with a "squaring" appearance of the foot. You are unable to pinch skin on dorsum of foot at second toe. What is the most likely diagnosis?

A. Deep vein thrombosis

B. Secondary lymphedema

C. Myxedema

D. Venous stasis

E. Hypoalbuminemia secondary to prostate cancer

ANSWERS

60.1 A. In lymphedema, diuretics unfortunately have little impact. Management options include support, pneumatic compression, manual lymph drainage, and surgery. In venous insufficiency, horse chestnut seed extract can be used to decrease signs and symptoms. Loop diuretics can be used short term to decrease edema burden.

60.2 C. Patients older than 45 with lower extremity edema and systemic signs such as fatigue, somnolence, and constipation could benefit from an evaluation for systemic disease as a cause for lower extremity swelling. A CBC, basic metabolic profile (BMP), urinalysis (UA), TSH, and serum albumin would be reasonable in this patient. Sleep studies and an echocardiogram would also be useful due to the increased risk for pulmonary hypertension as a cause of edema in patients older than 45 years. Liver function tests would be useful in patients who present with ascites. NSAIDs (5% risk of edema), calcium channel blockers ( 50% risk of edema), and oral contraceptives are medications that are associated with edema. The most common cause of unilateral edema without pain with onset more than 72 hours is venous insufficiency. Patients who cross their legs predominantly on one side can have greater disparity in leg swelling and varicosities.

60.3 B. The most common cause of lymphedema is secondary to malignancy (prostate, ovarian, lymphoma), surgery, and radiation therapy. The positive Kaposi Stemmer is seen in lymph edema. Chronic bilateral lower extremity swelling is unlikely to represent a DVT. Myxedema is associated with thyroid disorders. Hypoalbuminemia is seen in advance malignancies, nephrotic syndrome, protein-losing enteropathies, and liver disease.

CLINICAL PEARLS

⯈ Idiopathic edema and venous insufficiency are the most common causes of lower extremity swelling in patients without systemic disease and often can be diagnosed with history alone.

⯈ Pulmonary hypertension secondary to sleep apnea should be considered in patients presenting with leg swelling who are older than 45 years, have a neck circumference greater than 17 in (42 cm), have daytime somnolence, and a history of snoring.

⯈ If there is an unclear etiology of the lower extremity swelling, lipidema and lymphedema should be ruled out.

⯈ Options for anticoagulation in the treatment of DVT include low molecular- weight heparin, warfarin, and direct Xa inhibitors.

REFERENCES

Braunwald E, Loscalzo J. Edema. In: Kasper D, Fauci A, Hauser S, et al., eds. Harrison's Principles of Internal Medicine. 19th ed. New York, NY : McGraw-Hill Education; 2015. Available at: http:// accessmedicine.mhmedical.com. Accessed May 25, 2015. 

Buller HR, Prins MH, Lensin AW, et al. EINSTEIN-PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl] Med. 2012;366(14):1287-1297. 

Eberhardt RT, Raffetto JD. Chronic venous insufficiency. Circulation. 2014;130:333-346. 

Pittler MH, Ernst E. Horse chestnut seed extract for chronic venous insufficiency. Cochrane Database Syst Rev. Nov 14 2012;11:CD003230. 

Raju S, Neglen P. Chronic venous insufficiency and varicose veins. N Engl] Med. 2009;360:2319-2327.

HomeFamily Medicine Case FileLower Extremity Edema Case File