Version July 2025
INTRODUCTION —
Lymphedema is defined as the abnormal accumulation of interstitial fluid and fibroadipose tissues resulting from reduced lymph transport because of injury, infection, cancer/cancer-related treatment, or congenital abnormalities of the lymphatic system.
The clinical features, diagnosis, evaluation, and differential diagnosis of lymphedema are reviewed. The pathophysiology and etiology of lymphedema and treatment of lymphedema are reviewed separately. (See "Pathophysiology, classification, and causes of lymphedema" and "Management of peripheral lymphedema" and "Surgical treatment of primary and secondary lymphedema".)
RISK FACTORS —
The main risk factors for the development of lymphedema include certain hereditary syndromes, genetic mutations, malignancy and its treatments, obesity, infection, and trauma (table 1). Some factors (eg, obesity) contribute to an increased likelihood of worsening symptoms in patients already affected with lymphedema. (See "Pathophysiology, classification, and causes of lymphedema", section on 'Causes of lymphedema'.)
HISTORY —
A careful medical history is important in the evaluation of the patient with suspected lymphedema [1,2]. Components of the history that should be addressed include the age of lymphedema onset, areas of lymphedema involvement, associated symptoms, details of the progression of symptoms (eg, pain, swelling, tightness), medical history (eg, malignancy, radiation treatment), history of trauma, history of infection, surgical history (eg, lymph node dissection), travel history, and family history [3]. Current and previous treatment modalities should also be noted. Some patients may have a history of diuretic use, which is generally ineffective for lymphedema treatment.
Following treatment for cancer, the onset of lymphedema is usually insidious and typically characterized by slowly progressive swelling of an arm following axillary node dissection or a leg following inguinal node dissection [2,4]. In a systematic review that included nearly 30,000 patients, the incidence of upper extremity lymphedema was highest in the first two years following cancer treatment [5]. Risk varied based on the nature of the treatment, and the mode of diagnosis and was lower for those diagnosed clinically compared with using self-assessment. Among patients being treated for malignancy, methods for early identification have been suggested to identify and treat patients to minimize the progression of lymphedema [6].
Affected patients may initially experience aching pain in the affected limb. A feeling of heaviness, tightness, and discomfort commonly accompanies swelling. The swelling may first be apparent only in the proximal portion of the limb, or it can affect only a portion of the distal limb, including the digits. It may also include the corresponding quadrant of the trunk. As an example, a patient with breast cancer may complain of swelling over the ipsilateral breast and/or upper chest wall.
With chronic lower extremity lymphedema, large amounts of subcutaneous tissue may form, the genesis of which is incompletely understood. Because of the increased weight, patients can develop a restricted range of motion in the affected limb, which may limit their ability to perform activities of daily living and can affect body image.
Some patients, particularly older patients or patients with obesity, can have no symptoms and lymphedema can present as swelling that is apparent on measurement only.
PHYSICAL EXAMINATION —
The physical examination should assess swelling and skin changes and include palpation of the lymph nodes. A complete vascular evaluation should be performed to evaluate for other causes of limb swelling. (See 'Differential diagnosis' below.)
Two-thirds of cases of lymphedema are unilateral, although laterality depends on the precipitating event [7]. As an example, an axillary node dissection will increase the risk of lymphedema in the ipsilateral upper extremity, while a pelvic node dissection increases the risk of bilateral lower extremity lymphedema. The physical examination includes an assessment of the skin, soft tissues, and vascular system of the affected limb(s) [1].
If primary lymphedema is suspected [8-11], evaluation should include documentation of any physical signs or congenital anomalies associated with an inherited condition. (See "Pathophysiology, classification, and causes of lymphedema", section on 'Etiologic classification'.)
Examples include:
●Short stature (Turner syndrome) (see "Turner syndrome: Clinical manifestations and diagnosis")
●Port wine birthmarks or hemangiomas (Klippel-Trenaunay-Weber syndrome) (see "Klippel-Trenaunay syndrome: Clinical manifestations, diagnosis, and management")
●Shield chest (Turner syndrome, Noonan syndrome) (see "Noonan syndrome" and "Turner syndrome: Clinical manifestations and diagnosis")
Limb swelling — At the onset, swelling associated with lymphedema is typically characterized as "soft" and "pitting" in the affected limb. Pitting reflects the displacement of the excess interstitial water in response to pressure. Testing for pitting involves applying firm pressure to the edematous tissue for at least five seconds. If an indentation remains after the pressure is released, pitting edema is present. Pitting is variable in patients with lymphedema. It may be present early on but is generally absent with progressive lymphedema and will not occur with later stages of lymphedema. With worsening lymphedema severity, the skin becomes dry and firm with less pitting due to subcutaneous fibrosis and adipose deposition. Other changes become clinically apparent including dermal thickening, cobblestoning, and skin overgrowth (ie, hyperkeratosis), which can lead to verrucous (ie, wart-like) and vesicular skin lesions (eg, lymphostatic verrucosis, lymphostatic papillomatosis).
Dorsal hand and foot swelling. The presence of dysmorphic toes, transverse digital creases, and hypoplastic or upturned ("ski-jump") toenails is more indicative of primary lymphedema [12]. But while primary lymphedema is typically associated with marked foot/toe swelling and dysmorphic features, different primary lymphedema phenotypes may have varying degrees of foot swelling, and some patients with primary lymphedema can have foot sparing.
The inability or failure to pinch or pick up a fold of skin (ie, Stemmer sign) is indicative of lymphedema of the lower extremity [1,10]; however, a negative Stemmer sign does not rule out lymphedema. A positive Stemmer sign is characterized by a thickened skin fold at the base of the second toe. The examiner's inability to lift the skin of the affected limb compared with the contralateral limb is a positive sign. It is also described as difficulty lifting the skin of the dorsum of the fingers or toes of the affected limb. A positive Stemmer sign can be found in any stage of lymphedema.
Extremity measurements
Limb circumference — Circumferential measurements of the affected and contralateral lower extremity are a simple and inexpensive method to estimate edema.
Measurements of limb circumference and volume can aid the diagnosis of lymphedema, with circumference values used to calculate limb volume using the truncated cone formula (see 'Limb volume' below). Most lymphedema clinicians have abandoned simple circumferential measurements as it is less sensitive and underestimates lymphedema.
Measurements should be taken from the affected as well as unaffected contralateral extremity for comparison. Extremity measurements should be taken during the initial evaluation and during follow-up visits to assess the status of the disease and to monitor responses to therapy (ie, pre- and post-treatment measurements) [1].
Limb circumference measurements can be taken at any point on the leg, as long as the clinician is using anatomic landmarks to provide consistent measurements [13,14]. Specific measurement sites are used for estimating limb volume. (See 'Limb volume' below.)
Simple circumferential measurements in the extremity can be made at four points in both the affected and contralateral extremities with the limb in a relaxed position [15]:
●For the upper extremity:
•At the metacarpal-phalangeal joints (if edematous)
•Around the wrist
•10 cm below the olecranon process
•10 cm above the olecranon process
●In the lower extremity
•At the metatarsal-phalangeal joints (if edematous)
•2 cm superior to the medial malleolus
•10 cm above the superior pole of the patella
•10 cm below the inferior pole of the patella
A difference of more than 2 cm between the affected and contralateral extremities is considered clinically significant. Simple measurements can also be used to classify the severity of lymphedema using the American Physical Therapy Association (APTA) classification system. (See 'APTA based on extremity girth' below.)
Changes in circumference may be more difficult to detect in patients with obesity. In addition, the upper extremities are subject to variation from side to side due to differences in muscle mass and hand dominance and the shifting of fluid proximally or distally due to arm positioning and/or compression.
Limb volume — Limb volume is estimated by using circumferential measurements at standard distances (eg, truncated cone model), optoelectronic volumetry (ie, perometry), or other three-dimensional methods for scanning the limb [16-19]. All methods of limb volume measurement are effective and accurate when properly performed [1,14]. Limb volume measurement by water displacement was once the primary method for assessing limb volume. While it can detect changes in limb volume of less than 1 percent, it is inconvenient, cumbersome, and no longer commonly used [14].
●Limb volume calculation with the truncated cone formula – With this technique, upper or lower limb measurements are performed at 4 cm intervals beginning at the wrist and ankle, respectively. The measurements are then converted to volume using the truncated cone formula [20]. Data suggest that volume measurement based on limb circumference correlates well with volume measurements made by water displacement [21-23].
●Optoelectronic volumetry – Optoelectronic volumetry (ie, perometry) uses infrared light to scan a limb and calculate highly accurate volumes but is expensive due to a high equipment cost. Volume can also be assessed using infrared and optoelectronic measurements. This technique uses infrared beams to scan the limb and calculate a volume. Optoelectronic volumetry method is more reliable than water displacement volumetry for the measurement of upper extremity lymphedema [13,24].
Bioimpedance spectroscopy — Another way to assess lymphedema is by using bioimpedance spectroscopy (BIS), which measures the resistance to the flow of electrical current in a limb [25,26]. Because lymphedema increases the fluid content of the tissue, it reduces the resistance to current flow. L-Dex is derived from measurements made using a proprietary device that compares the resistance in the unaffected and affected limbs. Most lymphedema clinicians would consider a score increase >7.5 as consistent with lymphedema, however, there is some debate and variability. A benefit of this measurement is that fluid can be detected as it starts to accumulate, even before it may be physically noticeable to a patient or provider [27]. An L-Dex score increase >6.5 from a baseline measurement is thought to be a predictor of lymphedema development. Whether BIS is more sensitive than volume measurements is debated.
Functional status — Functional status should also be assessed during the examination. Some functional observations for patients with lower extremity lymphedema may include limitation in walking distance or upstairs, use of an ambulation aid, inability to bend over to remove shoes/socks, and inability to make a forward stride. If functional limitations are observed, the patient should be referred to physical therapy for evaluation and treatment [27]. Validated questionnaires, such as the Lymphedema Life Impact Scale, may also be used to measure patient-reported functional impairments, as well as physical and psychosocial impairments caused by lymphedema [28].
Other manifestations — The presence of lymphedema can result in infectious complications and a rare form of sarcoma. It can also result in significant psychological comorbidity with a negative impact on quality of life.
●Skin infection – Lymphedematous skin is at risk for recurrent infections, including cellulitis, erysipelas, and lymphangitis [29,30]. Cellulitis is a well-described complication of lymphedema, particularly in patients who have undergone axillary or inguinal lymph node dissection [29,31]. Typical manifestations include local changes in the affected limb including erythema, pain, and tenderness. Less commonly, patients can present with evidence of skin infection and systemic symptoms such as fever and malaise. In rare cases, lymphedema-associated infections can result in life-threatening sepsis requiring urgent care and antibiotic treatment. Although skin infection is a complication, it is also a risk factor for both the onset and progression of lymphedema.
●Lymphangiosarcoma – A rare secondary malignant tumor, called lymphangiosarcoma, can occur in patients with chronic lymphedema. It is usually seen in patients with massive and protracted edema [32,33]. It has been described with primary lymphedema and chronic filarial lymphedema [34-36]. The tumor originates in vascular endothelial cells of the affected extremity with lymphedema, not the lymphatic vessels. It may initially appear as blue-red or purple skin lesions with a macular or papular shape. Multiple lesions are common and subcutaneous nodules may appear. Such skin lesions should be carefully evaluated in patients with chronic lymphedema.
●Psychological effects – Lymphedema results in psychological morbidity and reduced quality of life, including aspects of emotional, functional, physical, and social well-being [1,37]. Psychological problems seen in females with chronic lymphedema after treatment for breast cancer include anxiety, depression, sexual dysfunction, social avoidance, and exacerbation of existing psychiatric illness [38,39].
DIAGNOSIS —
A history and physical examination with typical clinical features consistent with lymphedema and limb measurements can often establish a diagnosis, particularly in most cases of secondary lymphedema. However, further imaging is used whenever the clinical evaluation does not yield a definitive diagnosis, which is more common in patients with primary lymphedema, those with suspected lipedema, or in cases where lymphatic obstruction (eg, due to tumor) is suspected. (See 'Further evaluation' below.)
Clinical diagnosis — The presence of lymphedema is usually suggested by the following findings [1]:
●Edema that is localized and characterized by slowly progressive ipsilateral swelling of an upper extremity following axillary node dissection (unilateral) or lower extremity following inguinal node dissection (unilateral or bilateral).
●A history of cancer treatment or trauma. Cancer treatments include surgical resection, sentinel lymph node biopsy or lymph node dissection (eg, axillary, inguinal lymph nodes), and radiation therapy.
●Absence of generalized edema etiology (eg, heart failure, nephrotic syndrome). Occasional patients have both lymphedema and generalized edema, such as cancer patients with an established diagnosis of heart failure who have undergone a lymphadenectomy, or the patient with obesity and longstanding chronic venous insufficiency. In these settings, lymphedema is suggested by asymmetry of the limbs.
●Presence of cutaneous and subcutaneous thickening, which is seen in severe lymphedema.
●Presence of nonpitting edema, which is suggestive of lymphedema, although pitting does not exclude lymphedema since it is present in the early stages of lymphedema. (See 'Limb swelling' above.)
Primary lymphedema should be suspected in a patient (typically female) who has no history of lymphatic injury (eg, trauma, surgery) and who presents with swelling in the lower extremity, often with one side worse than the other. The patient may also have a positive family history of lymphatic disease.
Clinical severity — Several systems are used to classify the severity of lymphedema as mild (grade or stage I), moderate (grade or stage II), or severe (grade or stage III) based on the physical condition of the extremity (eg, limb girth, limb volume, skin changes) (picture 1). The clinical severity of lymphedema informs the approach to treatment. (See "Management of peripheral lymphedema", section on 'Intensity of treatment'.)
Using the International Society of Lymphology (ISL) criteria (table 2), lymphedema is staged based on the examination of the lower extremity and the volume difference between the extremities as stage 0 through stage III, which corresponds to subclinical lymphedema, mild lymphedema, moderate lymphedema, and severe lymphedema [1]. Several other classification systems are also used to describe the severity of lymphedema, including the American Physical Therapy Association (APTA) [40], the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) [41], and the Campisi staging system (table 3), which stages lymphedema from stage 1 to stage 5.
These classification schemes generally only refer to the physical condition of the extremity. Classifications including physiologic or genotypic information are evolving.
ISL clinical stage — We suggest using ISL's staging system to characterize the severity of lymphedema (table 2) [1]. ISL combines two criteria to diagnose and classify lymphedema: the "softness" or "firmness" of the limb (reflecting fibrotic soft tissue changes) and the outcome after elevation. Stage 0 lymphedema is a subclinical or latent condition where swelling is not evident despite impaired lymphatic transport. Within stages I through III, severity is based upon volume differences, which are assessed as mild (<20 percent increase), moderate (20 to 40 percent increase), or severe (>40 percent increase).
●Stage 0 – Stage 0 (or Ia) lymphedema is a subclinical or latent condition where swelling is not yet evident despite impaired lymph transport. There are subtle alterations in tissue fluid/composition and changes in subjective symptoms. Most patients are asymptomatic, but some report a feeling of heaviness in the limb. Stage 0 can be transitory or may exist months or years before overt lymphedema occurs (ie, stage I, II, or III below).
●Stage I – Stage I lymphedema (picture 2) represents an early accumulation of fluid relatively high in protein content (in comparison with "venous" edema) and subsides with limb elevation or wrapping. Pitting may occur. This is sometimes called reversible edema. Stage I corresponds to a mild grade of lymphedema.
●Stage II – Stage IIa lymphedema (picture 3) is associated with fat hypertrophy and fluid accumulation. This results from adipose cell proliferation in response to interstitial fluid stasis. As a result, wrapping or limb elevation is much less effective for the reduction of limb swelling. As lymphedema progresses to Stage IIb, there is progressive fibroadipose tissue deposition and often skin thickening that is irreversible even with continuous compression. This stage of the disease is sometimes called spontaneously irreversible lymphedema.
●Stage III – Stage III lymphedema (picture 4) encompasses lymphostatic elephantiasis where pitting can be absent and trophic skin changes such as acanthosis, alterations in skin character and thickness, further deposition of fat and fibrosis, and warty overgrowths have developed. Stage III corresponds to a severe grade of lymphedema. It should be noted that a limb may exhibit more than one stage, reflecting alterations in different lymphatic territories.
APTA based on extremity girth — The APTA uses girth as an anthropometric measurement to classify lymphedema. The maximum girth difference between the affected and unaffected limb (typically upper extremity) is used to determine the class of lymphedema [40]:
●Mild lymphedema – Maximum girth difference <3 cm
●Moderate lymphedema – 3 to 5 cm difference
●Severe lymphedema – Difference >5 cm
The ISL notes that some clinicians use volume differences between the affected limb and the normal contralateral limb (equally applicable to upper and lower extremities) to define the severity of lymphedema as mild: volume difference >10 percent but less than <20 percent; moderate: volume difference 20 to 40 percent; and severe: volume difference >40 percent [1].
NCI clinical grade — The NCI's CTCAE categorizes lymphedema based upon examination findings and the presence of functional impairment [41]. These correspond roughly to the clinical stages described below.
●Grade 1 – Trace thickening or faint discoloration
●Grade 2 – Marked discoloration, leathery skin texture, papillary formation, moderate symptoms limiting instrumental activities of daily living
●Grade 3 – Severe symptoms limiting self-care and activities of daily living
DIFFERENTIAL DIAGNOSIS —
The differential diagnosis of lymphedema is broad and differentiated by the distribution of the edema. (See "Clinical manifestations and evaluation of edema in adults".)
The main conditions associated with peripheral edema that might be confused with lymphedema (picture 5) in either the upper or lower extremities include:
●Venous obstruction
•Acute venous obstruction – Classic symptoms of acute deep venous thrombosis (DVT) include acute swelling, pain, and erythema involving one limb. The onset of edema and the associated symptoms (eg, acute erythema, limb pain) readily distinguish acute DVT from lymphedema. (See "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity".)
Post-thrombotic syndrome is the development of chronic venous insufficiency following DVT. A prior history of DVT can distinguish this condition from lymphedema. (See "Post-thrombotic (postphlebitic) syndrome in adults".)
•Chronic venous insufficiency – Extremity swelling resulting from chronic venous outflow obstruction can have a gradual onset. Edema, particularly in the lower extremities, is worse with limb dependency and improved with limb elevation, which distinguishes it from lymphedema. The patient may also experience limb pain with activity (ie, venous claudication). Lymphedema is further distinguished from chronic venous insufficiency by an absence of typical varicose veins, and an absence of characteristic skin change distribution (eg, brawny discoloration at the medial ankle in chronic venous insufficiency, venous leg ulcer). Duplex ultrasound will demonstrate typical findings of venous valvular insufficiency. (See "Clinical features, diagnosis, and classification of thoracic central venous obstruction" and "Clinical manifestations of lower extremity chronic venous disorders" and "Overview of iliocaval venous obstruction", section on 'Clinical features' and "May-Thurner syndrome".)
However, a subset of patients with longstanding and severe chronic venous insufficiency may develop lymphedema (picture 6) [42]. (See "Pathophysiology, classification, and causes of lymphedema", section on 'Chronic venous insufficiency'.)
●Lipedema – Lipedema is an adipose disorder characterized as the abnormal deposition of fat with associated edema in females [43-45]. A pedigree analysis suggests it is inherited as an X-linked dominant or autosomal dominant condition [46]. Patients with lipedema have a symmetric disproportional accumulation of fat and pain in the affected tissues. Patients with lipedema will generally not have a history of inciting factors (eg, lymph node resection, trauma). Elevating the limbs has no effect on limbs with lipedema. The feet are usually not involved with lipedema, but the feet may or may not be involved in lymphedema. If a question remains, lymphatic imaging can help clarify the diagnosis (algorithm 1). Patients with lipedema usually have normal lymphatic function. (See "Diagnosis and management of lipedema" and 'Lymphatic imaging' below.)
●Limb hypertrophy – Rarely, some syndromes are characterized by limb size discrepancies that may be due to hypertrophy of the soft tissue and bones (ie, Klippel-Trenaunay syndrome), or overgrowth of body parts in a disproportionate fashion (ie, Proteus syndrome), that may affect one or more limbs (typically lower extremity) [47,48]. These syndromes are associated with other clinical manifestations, such as capillary malformations, which may help to distinguish them from lymphedema. (See 'History' above.)
●Myxedema – Myxedema results from infiltration of the skin by glycosaminoglycans with associated water retention leading to nonpitting edema. (See "Clinical manifestations of hypothyroidism", section on 'Skin'.)
FURTHER EVALUATION —
Although a diagnosis of lymphedema is usually clinically apparent based on history, physical examination, and extremity measurements, additional evaluation can help identify an etiology for lymphedema if it is not clinically apparent and distinguish lymphedema from nonlymphatic causes of edema. Other evaluation using magnetic resonance (MR) imaging/angiography or genetic testing may be useful in select patients. (See "Pathophysiology, classification, and causes of lymphedema", section on 'Causes of lymphedema' and 'Differential diagnosis' above.)
Patients in endemic areas should be tested for filarial infection.
Vascular and soft tissue imaging
●Duplex ultrasound – Duplex ultrasound should be obtained on any patient with lower extremity edema to evaluate the patency of the venous system (ie, identify venous thrombosis or stenosis) and identify the presence of venous reflux.
The grayscale (B-mode) evaluation of tissue layers in the affected limb can also provide information on the etiology, as well as the severity of lymphedema [49]. Ultrasound directly aids in the diagnosis by identifying tissue alterations or any mass that might be the cause of lymphatic compression [1]. Following treatment of cancer, an onset of limb swelling several years after the primary surgery without obvious trauma may be indicative of a recurrent tumor. In particular, recurrence of breast cancer in the axillary area or the development of lymphangiosarcoma should be sought [50-52].
●Advanced cross-sectional and vascular imaging – Cross-sectional imaging using MR, or alternatively computed tomography (CT) imaging, can also demonstrate the accumulation of fluid within soft tissues of the extremity with good sensitivity [53,54]. In patients with suspected lymphedema, MR may be more commonly used; however, this varies with institutional resources and the availability of interpretation. Common findings in patients with lymphedema include circumferential edema, increased volume of subcutaneous tissue, marked thickening of the dermis, and thickened perimuscular aponeurosis. It is important to note that while imaging of the extremity can detect the presence of increased interstitial fluid (honeycomb appearance), this finding is nonspecific and does not directly indicate the grade of lymphedema [14]. Cross-sectional imaging may also identify enlarged lymph nodes, tumor recurrence, or other lesions that can cause lymphatic obstruction [16]. MR can further differentiate the cutaneous edema of lymphedema from other types of limb swelling such as lipedema and lymphedema related to chronic venous insufficiency. MR venography identifies the presence of stenotic venous lesions. This is an important finding as it impacts potential future surgical options (eg, lymphovenous bypass, lymph node transplant) and was identified in 15 percent of patients in one review [16].
Lymphatic imaging — The diagnosis of lymphedema does not typically require lymphatic imaging; however, most patients with new onset disease following surgery benefit from lymphatic imaging to confirm the diagnosis, characterize the stage of lymphedema, and aid with monitoring. For patients suspected of having primary lymphedema, lymphatic imaging studies are instrumental in confirming the diagnosis. For patients with secondary lymphedema, imaging studies are useful for determining the severity of lymphedema and whether any functional lymphatics are present, which determines candidacy for lymphatic reconstruction. (See "Management of peripheral lymphedema" and "Surgical treatment of primary and secondary lymphedema".)
Imaging modalities that have been used in the diagnostic evaluation of lymphedema include lymphoscintigraphy, CT, MR imaging/MR lymphography, and indocyanine green (ICG) lymphangiography. Each of these lacks standardization of techniques, resulting in variable results. The protocols used for lymphoscintigraphy can be highly variable. Nevertheless, in centers that specialize in lymphatic disorders, protocols that use varying techniques can depict the specific lymphatic dysfunction.
●Lymphoscintigraphy – Lymphoscintigraphy images the flow of macromolecules and interstitial fluid from the skin to the lymph nodes, particularly in the extremities [4,55]. Lymphoscintigraphy primarily evaluates larger superficial lymphatic vessels and nodes but does not provide information on the deep transport lymph vessels. Subcutaneous or intradermal radioactive tracers are injected in the dermis of the extremity, and imaging is performed 30 to 120 minutes after injection. The patient then performs a stress activity (such as walking, massage, or squeezing a ball for approximately 20 minutes), which is followed by repeat imaging.
•For the lower extremity, lymphoscintigraphy is the primary imaging study used for diagnosing and assessing the function of lower extremity lymphatics. The radioactive tracer is typically injected into the dermis of the foot.
•For the upper extremity, lymphoscintigraphy may be obtained prior to lymphatic surgery to identify any functional lymph nodes so that injury to them can be avoided during lymph node transplantation.
Criteria for impaired lymphatic function for qualitative lymphoscintigraphy include abnormal lymphatic uptake, slow or absent lymphatic flow, asymmetric or absent visualization of the regional lymph nodes, and dermal backflow. While quantitation of regional lymph node accumulation of the tracer appeared to be more sensitive compared with qualitative lymphoscintigraphy (100 versus 70 percent in a series of 219 patients with secondary or primary lymphedema [56]), it is rarely performed due to the time to acquire the scans and specialized protocols. Most cases that would not otherwise be captured with qualitative lymphoscintigraphy are mild grade I disease.
●ICG lymphangiography – ICG lymphangiography is a technique in which a near-infrared dye (indocyanine green) is injected intradermally. The dye is bound by albumin after injection, and uptake is therefore restricted to the lymphatics. The lymphatic vasculature can then be directly imaged with specialized sensors. Lymphatic vessel anatomy, leaking, pumping capacity, and dermal reflux can all be seen. Like MR lymphangiography, ICG lymphangiography is mainly used for preoperative mapping. Many lymphatic surgeons rely on ICG imaging for staging of lymphedema and identifying patent lymphatic channels, which is crucial for surgical interventions like lymphovenous bypass [57,58]. (See "Surgical treatment of primary and secondary lymphedema", section on 'ICG lymphangiography'.)
●MR lymphangiography – For demonstrating the lymphatic channels, MR has many advantages; however, the injected contrast material taken up by the lymphatics is also taken up by nearby veins. The lymphatics are typically beaded in appearance in comparison with the veins and have a higher signal intensity, but judgment is needed to distinguish them. Specialized MR techniques are being developed to exclude venous uptake, but these are not widely available [59]. MR lymphangiography is typically used for mapping the lymphatic system before surgery, rather than for diagnostic purposes. It is essential to identify patent (open) lymphatic channels before performing lymphovenous bypass. MR lymphangiography provides detailed images of the lymphatic vessels, helping surgeons plan their procedures effectively. (See "Surgical treatment of primary and secondary lymphedema", section on 'MR lymphangiography'.)
Genetic testing — For patients diagnosed with primary lymphedema or suspected of lymphedema tarda, referral to a medical geneticist or genetic counseling service is suggested for evaluation of the family history and recommendations for further workup [60]. (See "Genetic testing".)
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: Lymphedema".)
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 variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Lymphedema (The Basics)")
●Beyond the Basics topics (see "Patient education: Lymphedema after cancer surgery (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Lymphedema – Lymphedema is a progressive disorder of the lymphatic system that results in the accumulation of interstitial fluid and fibroadipose tissue. (See 'Introduction' above.)
●Clinical features – Patients with peripheral lymphedema classically present with slowly progressive unilateral swelling of the affected limb. They may also have skin changes, limb pain and discomfort, and restricted range of motion. With worsening lymphedema severity, dermal thickening, cobblestoning, and skin overgrowth (ie, hyperkeratosis) occur. Clinical findings suggestive of lymphedema include (see 'History' above and 'Physical examination' above):
•History of cancer treatment or trauma
•Absence of generalized edema
•Presence of cutaneous and subcutaneous thickening
•Presence of nonpitting edema (may have pitting edema early on)
●Diagnosis and clinical severity – The diagnosis of lymphedema is generally made by history, physical examination, and comparison of extremity measurements (eg, limb volume) of the affected with the unaffected limb. We use the International Society of Lymphology (ISL) classification, which uses a combination of clinical features to stage the limb as subclinical, mild, moderate, or severe lymphedema (table 2). (See 'Diagnosis' above.)
●Differential diagnosis – The differential diagnosis of lymphedema includes acute or chronic venous obstruction, lipedema, peripheral edema due to systemic illness or other causes, and limb hypertrophy. Clinical manifestations such as acute limb pain, dependent edema, erythema, varicosities, ulceration, lack of foot involvement, and demonstration of normal lymphatics differentiate these from lymphedema. (See 'Differential diagnosis' above.)
●Further evaluation – We obtain duplex ultrasound on all patients who present with limb swelling to rule out venous obstruction as the cause of swelling. Imaging of the lymphatic system is usually not necessary to confirm the diagnosis of lymphedema but can help identify an etiology for lymphedema if it is not clinically apparent and can distinguish lymphedema from nonlymphatic causes of edema. Lymphoscintigraphy is the primary imaging modality used. Further evaluation using soft tissue imaging or genetic testing may be useful in select patients. (See 'Differential diagnosis' above and 'Further evaluation' above.)
ACKNOWLEDGMENT —
The editorial staff at UpToDate acknowledge Emile R Mohler, III, MD, who contributed to an earlier version of this topic review. UpToDate also acknowledges Dr. Mohler's work as our Section Editor for Vascular Medicine.
