Lower extremity edema is a symptom that is observed prevalently worldwide. It arises when the volume of fluid in the lower extremities exceeds the capacity of the tissues to accommodate it physiologically. The peripheral lympho-vascular system has a physiologically balanced pressure gradient between hydrostatic pressure, oncotic pressure, and interstitial fluid pressure. If the pressure gradient is disrupted (interferes with), excessive interstitial fluid accumulates, leading to peripheral edema. In some cases, adipose tissue accumulation can be observed as edema. Fluid retention can occur in numerous situations, and conditions that disrupt the venous blood flow in the lower limbs or lymphatic circulation may be the underlying causes (1).

Lower extremity edema is a common clinical manifes-tation; however, its diagnosis is occasionally demanding. Unilateral edema may initially suggest venous or lymphatic disorders. Bilateral symmetrical edema may indicate systemic disease. However, bilateral asymmetric edema can have different causes in each leg or may be due to overlapping systemic diseases. Lymphedema and venous edema can be asymmetrical or symmetrical in both the lower extremities. Evaluating the duration is also important, as acute edema (<72 h) may be mainly due to deep vein thrombosis (DVT), infection, trauma, or worsening of congestive heart failure. Chronic edema is likely to occur because of venous insufficiency, lymphatic disorders, musculoskeletal diseases, or underlying chronic medical conditions. Edema due to venous diseases typically worsens in the evening and is often associated with leg pain, heaviness, and fatigue. Lymphedema is generally painless and may exhibit classic skin changes owing to foot involvement. Localized painful swelling may indicate musculoskeletal or joint disorders. However, these clinical findings may not always be consistent (1,2).

Various medical conditions can cause lower extremity edema, and it is important to rule out systemic diseases that can cause leg edema. If there is no related systemic disease and the patient’s leg edema persists despite proper medical treatment, further examinations, such as lower-extremity ultrasonography, should be performed to differentiate peripheral vascular diseases (3). Even now, patients are not able to receive appropriate medical advice when they have experienced lower extremity edema, and more importantly, their practitioners may underestimate the leg edema of the patient if they do not specialize in lower leg conditions. In this study, we aimed to analyze the clinical data of patients with lower extremity edema and share the results, which may remind us of the role of vascular specialists.

From January 1, 2019, to September 30, 2019, we conducted a retrospective study on patients who initially visited our vascular surgery outpatient clinic for lower extremity edema. This study was approved by the Institutional Review Board. In total, 112 medical records were reviewed.

We referred to the algorithm for leg edema proposed by Ely (2). History taking is a significant part of the clinical diagnosis of lower extremity edema and should include hypertension, diabetes, chronic kidney disease, deep vein thrombosis (DVT), varicose veins (VVs), medication history, musculoskeletal disorders (MSD), trauma, and pelvic or leg surgery.

We recorded the duration of edema with a cut-off setting of 72 h, which was acute (<72 h) or chronic (>72 h). We also recorded whether the edema was unilateral, bilateral, pitting, or non-pitting. We checked whether the patients had shortness of breath or dyspnea during exercise, habitual prolonged standing or walking, the presence of accom-panying pain, and other relevant information regarding whether the edema persisted or improved after waking up. Varicose veins, ulcers, and skin changes were recorded. Blood tests were performed to exclude systemic diseases. In cases of acute edema, D-dimer and lower extremity Doppler ultrasonography were performed. Lymphoscinti-graphy was performed if lymphedema was suspected. If the patient was presumed to have heart disease, we performed chest radiography, electrocardiography, and echocardio-graphy with our consultant cardiologists. We proposed a final diagnosis based on the medical history, physical examination, laboratory tests, imaging studies, and consul-tation with other specialists.

Among the 112 patients, 42 (37.5%) patients were diagnosed with chronic vascular disease (CVD group). Overall, 28 (25%) patients had no clearly identified causes and were considered idiopathic (idiopathic group). Another 28 (25%) patients had musculoskeletal disorders (MSD group) and 10 (2.9%) patients had chronic conditions and systemic disease (MD group). There were 4 isolated cases of dermatitis, insect bites, pregnancy, and morbid obesity (Misc group) (Table 1).

Table 1 . Clinical diagnosis of leg edema (2019.01.01∼09.30, N=112).

Vascular Dz.	N=42 (37.5%)	Musculo-skeletal	N=28 (25%)
VVs	24 (21.4%)	HIVD	7
Lymphedema	9	DJD, knee	7
DVT	5	Sciatica	3
PTS	1	Tendinitis	3
Iliac vein occlusion	2	Hematoma	2
STP	1	Meniscus tear	1
Medical Dz.	N=10 (8.9%)	Sprain	1
General edema	5	ECS	1
DKA	1	Ganglion	1
CHF＋CKD	1	Etc.	N=4 (3.5%)
CKD	1	Contact dermatitis	1
Arrythmia	1	Sting bite	1
Medication	1	Pregnancy	1
Non identified*	N=28 (25%)	Morbid obesity	1

*Nonidentified groups were treated for idiopathic cyclic swelling..

Seventy patients (62.5%) in the CVD and idiopathic groups were treated using a combination of phlebotonics and compression therapy. In the idiopathic group, phlebo-tonics were administered to 11 patients and stockings were used in 14 patients. Among the 24 patients with varicose veins, eight patients were treated with medication and seven patients were treated with compression stockings. All 9 patients with lymphedema used phlebotonics, and 4 patients additionally used compression stockings. Phlebotonic stockings were used in two patients with post-thrombotic syndrome (PTS), and compression stockings were used in two patients. More than half of the patients experienced symptomatic relief (Table 2). The remaining 42 individuals assigned to the MSD, MD, or Misc groups received optimal care from specialists (Fig. 1).

Table 2 . Clinical outcomes of the treatment of leg edema.

Diagnosis	No of Pts	Phlebotonics	＋Stocking	Mean FU	Outcome
Not identified*	28	11	14	377 days	Cure 3, improved 12, fail 1, FU loss 11
VVs**	24	8 (no surgery)	7	255 days	Improve 5, fail 3
Lymphedema	9	9	4	315 days	Cure 1, improved 4, fail 1, FU loss 3
DVT, PTS	4	2	2	389 days	Improved 2, fail 1, FU loss 2

*Nonidentified groups treated for chronic venous insufficiency..

**8 non-surgical patients with VVs is included in this Ttable..

Figure 1. Clinical diagnosis of leg edema (N=112). *No clearly identified causes were considered idiopathic group.

Overall, 24 cases (21.4%) of the 112 patients were diagnosed with lower-extremity varices, with 17 (15.2%) patients showing reflux in the saphenous vein on Doppler ultrasound. Among the 24 patients, 10 patients underwent varicose vein surgery, eight patients received conservative treatment, such as medication and compression stockings, and six patients were lost to follow-up. Among the 8 patients who received conservative treatment, 5 patients showed improvement in symptoms, whereas 3 patients did not show improvement in symptoms (Fig. 2).

Figure 2. Flow chart for treatment in patients with varicose veins.

Among the patients who visited the outpatient clinic for lower extremity edema, chronic venous disease was the most common cause, accounting for 37.5% of the cases. Diagnoses included varicose veins, lymphedema, deep vein thrombosis, post-thrombotic syndrome, iliac vein occlusion, and thrombophlebitis. This finding is consistent with the results of the Edinburgh Vein Study, which reported a prevalence rate of 37.9% for chronic venous diseases, including varicose veins, similar to the findings of this study (4). According to a survey conducted on 1166 general individuals in South Korea, 32.3% of the respondents reported having experienced chronic venous diseases of C3 severity or higher (5). The next most common cause was musculoskeletal disorders, accounting for 25% of cases. Immobility owing to conditions, such as spinal stenosis or joint disease is considered a major cause of swelling in musculoskeletal disorders, along with other causes, such as hematoma, muscle tearing, and ganglions. Systemic disease- related edema accounted for 9% of the cases, and other causes accounted for 3.5%. Systemic disease-related edema included cases in which the swelling was caused by preexisting (5 cases) or newly diagnosed conditions (5 cases). Other causes included dermatitis, pregnancy, obesity, and sting bites. Finally, 28 cases (25%) were identified as idiopathic edema without an identified cause and were treated based on chronic venous insufficiency.

The most common single disease associated with lower limb edema was varicose veins, which accounted for 24 cases (21.4%). Varicose veins accompanied by symptoms may require surgical treatment, whereas those accompanied by edema should be evaluated for other potential causes before treatment. The 2022 European guidelines also recommend considering nonvenous causes of edema in patients with clinical class C3 disease (Recommendation 16, Class IIa, Level of Evidence C) (6). If lower limb edema is present in patients with saphenous vein reflux and no superficial vein dilatation is observed, if it is bilateral, or if there are other concurrent diseases related to edema, there may be a possibility that the edema will not improve with varicose vein surgery. In contrast, venous surgery may be expected to be effective in patients with concomitant varicose veins and edema (Clinical class C2, 3 s), especially in cases of unilateral lower limb edema (6). The 2020 Appropriate Use Criteria also address C3 edema separately. The panel mentioned that edema can be associated with various causes. They considered it rare for reflux and edema to coexist without visible protruding veins and mentioned that edema may or may not improve with venous treatment. They also noted that there are limited data on the treatment effect of edema when only below-knee great saphenous vein (GSV) reflux or segmental reflux is present (7). Treatment for segmental reflux is generally unnecessary, even in the absence of edema (8). There seems to be a difference in perspectives regarding clinical class C3. Some researchers consider C3 a separate entity, whereas others consider it a more severe symptom of venous disease than C1 and C2, warranting further treatment. In this study, surgical treatment was performed in 10 of 24 venous patients with visible protruding veins and reflux, while the remaining eight patients underwent non-surgical treatment, with an improvement in edema observed in five cases. Differen-tiating between venous and non-venous causes of edema can be challenging because venous-related edema can coexist with other non-venous causes. However, it is advisable to follow these guidelines and confirm the absence of other underlying causes before deciding to perform venous surgery.

Similar results were observed in the Edinburgh Vein Study, with 14.1% of males and 24.6% of females with high-grade trunk varices presenting with leg swelling. However, in the Edinburgh study, 6.1% of males and 17.6% of females presented with leg swelling without trunk varices (9). Furthermore, the incidence of reflux was reported to be 12.7% in an Edinburgh study. The prevalence of reflux by vessel type was 8.8%, 2.6 %, and 1.3% for superficial vein, deep vein, and combined refluxes, respectively (10). In our study, among patients with lower limb edema, the incidence of superficial vein reflux was 15.2% (17/112), indicating that lower limb edema occurred independently of saphenous reflux in approximately 85% of cases, suggesting that superficial venous reflux may not be the main cause of edema.

The limitations of this study were as follows: First, this was a retrospective analysis of medical records and edema is known to be caused by multifactorial factors, which may indicate that the identified disease was not the sole cause of edema. Second, as the study targeted patients visiting the vascular surgery outpatient department for the first time, many patients may have visited the hospital with suspected vascular disease, leading to a possible selection bias. The grades of edema can be divided according to the degree of lower limb edema; however, owing to the nature of this retrospective study, the degree of edema could not be analyzed (11). Additionally, the follow-up period was relatively short (approximately 1 year). Nevertheless, this study has the following strengths: Screening tests and lower-extremity ultrasonography were conducted for patients with lower-extremity edema, and various diseases were diagnosed through consultations with related departments.

In this study, 37.5% of the patients with lower limb edema had CVD, 25% had idiopathic edema, 25% of patients had MSD, and 12.5% of patients had other medical conditions causing edema, indicating the need for interdisciplinary consultations and differential diagnoses. Although there are several patients with CVD, CVD treatment does not seem to have an absolute significance in the treatment of lower extremity edema. Therefore, vascular specialists play the role of a control tower in diagnosing CVD, drawing the most reasonable conclusions through cooperation with other specialists, and performing surgical treatments as needed. Among the patients with edema, 21.4% had concomitant varicose veins; however, only 15.2% showed reflux in the saphenous veins. The agreement between saphenous reflux and leg edema appears to be poor. Thus, saphenous vein reflux may not be the sole underlying cause of lower limb edema, and further differential diagnosis of other potential causes is necessary.

This study was presented at the 44th Conference of the Korean Society for Phlebology on April 02, 2023.

The authors declare no potential conflict of interest.