Routine Diagnostic Venous Ultrasound and LAS for Leg Edema of Unknown Cause

Abstract

Objective: To verify the diagnostic efficiency of venous duplex ultrasound and lymphangioscintigraphy (LAS) in establishing the cause of leg edema and to clarify the pathology of these leg edemas.

Materials and Methods: Between April 2009, and March 2010, 62 patients with leg edema of unknown origin were referred to the Edema Clinic of the Yamaguchi University Graduate School of Medicine. All patients underwent a venous duplex ultrasound scan and LAS.

Results: Of 62 patients, lymphatic insufficiency, venous insufficiency or both was diagnosed in 42 (68%), and lymphedema, in 29 (47%). Venous duplex ultrasound detected obvious venous disorders in only 13 (21%), and for 20 patients, the ultrasound and LAS did not reveal any abnormalities; however, for 15 of the 20 (24% of all patients), venous edema was attributed to functional causes.

Conclusion: Venous duplex ultrasound and LAS assisted in the diagnosis of leg edema of unknown origin and also proved useful in establishing treatment strategies.

Introduction

Though edema of the extremities, such as lymphedema, is a much studied area of research, patients suffering from edema have not benefited enough because of a lack of appropriate diagnostic and treatment guidelines. Edema, defined as swelling caused by an increase in the fluid content of the interstitium, which is physically recognizable,¹⁾ basically arises through an imbalance of ultrafiltration, diffusion, and reabsorption in the blood capillaries as described by the Starling equilibrium. The underlying condition resulting in an increased volume of ultrafiltration or diffusion, caused for example, by inflammation or hypoalbuminemia, is often detected by screening examinations, in which case, treatment options can be initiated. On the contrary, disturbed reabsorption, because of venous or lymphatic insufficiency, can only be diagnosed by specialists. Even though physicians can diagnose the condition, they often lack the training to provide the complex physical therapy required. Unfortunately, only a few clinics in Japan can provide a systematic diagnosis and treatment program for edema patients.

The Edema Clinic of the Yamaguchi University Graduate School of Medicine has been launched to provide standard treatment for patients with various types of edema, and many patients are referred to us. These patients suffer from serious venous insufficiency as well as lymphedema of the legs and often, their venous problems are functional rather than anatomical. Moreover, since lymphangioscintigraphy (LAS) is not commonly done in Japan, the diagnosis of lymphedema is only supported by indirect findings. We believe that both venous duplex ultrasound and LAS are essential for diagnosing these leg edemas. Thus, we conducted this study to verify the efficiency of using both these diagnostic tools to assist in the diagnosis of leg edema of unknown cause. We also tried to clarify the pathology of these leg edemas as a consequence of their diagnoses.

Patients and Methods

The subjects of this study were 62 patients, who were referred to our clinic with a tentative diagnosis of “leg edema of unknown origin,” between April, 2009 and March, 2010. They comprised 43 women and 19 men, ranging in age from 22 to 91 years (mean, 66 years).

The status of underlying disease that could be related to the formation of edema is summarized in Table 1. Of 62 patients, 44 (71%) suffered one or more of these edema-genic coexistent diseases. The prescription contents that could cause drug-induced edema are summarized in Table 2. Thirty-two (52%) patients were taking one or more of these medications.

All patients underwent blood examinations, chest X-ray, electrocardiogram, and cardiac ultrasound to detect signs of specific diseases causing edema. A venous duplex scan (ultrasound system with 7 and 11 MHz transducers; GE Yokogawa Medical, Kagawa, Japan) was done to reveal any kind of venous insufficiency, such as obstruction, stenosis, reflux, or dilatation of the deep/superficial veins, using an ultrasound system.^{2, 3)} An LAS was also done routinely to verify lymphatic insufficiency. Each patient was given an intradermal injection of 111MBq of ^99mTc suspended in 0.1 ml human serum albumin (^99mTc-HAS) into the first interdigital web. When the inguinal nodes and lymphatic trunks in the leg were not visualized within 1 hour after the injection, and/or there was congestion of the ^99mTc-HAS in the dermis (dermal back flow sign), we diagnosed reduced lymphatic function (Fig. 1).^{4, 5)}

Fig. 1.

Lymphangiography images of a 76-year-old woman with a history of hysterectomy for cervical cancer, 1 h after ^99mTc-HSA injection. Both iliac lymph trunks are absent because of lymphadenectomy. In the left leg, the lymph trunk (solid arrow) and inguinal nodes (dotted arrow) are enhanced without congestion of ^99mTc in the dermis, indicating normal lymphatic function. In the right leg, the lymph trunk and inguinal nodes are not visualized, with severe ^99mTc congestion in the dermis, being the dermal backflow sign (wide arrow), indicating impaired lymphatic function.

Results

The duration of leg edema, after presentation, ranged from 1 day to 25 years (median 3 months) as reported by each patient. The area of leg edema, which was confirmed by physical examination as pitting or by ultrasound as an echo-free space, is shown in Fig. 2. Forty-two (68%) patients had bilateral edema and most patients had edema in the peripheral parts of the leg. No association was found between these findings and lymphatic/venous insufficiency.

Fig. 2.

The existing part of leg edema.

Of 62 patients, we confirmed lymphatic insufficiency in 29 (47%), concomitant lymphatic insufficiency and venous insufficiency in 5 (8%) (Table 3), and venous insufficiency, confirmed by venous ultrasound, in 13 (21%). For the remaining 20 patients in whom no abnormality was found by venous ultrasound or LAS, we considered the edema to be caused by renal insufficiency in one, severe malnutrition in another, and liver failure in yet another (n = 3; 4%). One patient had lipedema and another patient was free of edema. The other 15 patients (24%) did not show a specific abnormality, even on other routine examinations. However, they all had skin lesions classified as C4 or greater by the CEAP classification (Fig. 3).^{6, 7)} These patients were aged 56 to 91 years (mean, 71 years) and had coexisting diseases that obviously disturbed their ambulation, including past leg surgery, osteoarthritis, congenital problems, or past cerebral infarction.

Fig. 3.

“Functional” venous insufficiency.

A: Photographs of a 77-year-old woman with osteoarthritis in both knees. She is wheelchair-bound most of the day. The edematous legs are complicated by congestive dermatitis and pigmentation.

B: Photographs of an 80-year-old woman with a history of congenital right hip dislocation, followed later by a right knee injury as a result of a traffic accident. The edematous legs look cyanotic (upper) and are complicated by a venous ulcer (lower).

Venous ultrasound and lymphangioscintigraphy showed no abnormality in either patient. Their symptoms improved remarkably after treatment with below-knee multilayered bandages, physical therapy to improve the range of motion of the ankles, and calf muscle training.

Discussion

In the current study of patients referred to us with leg edema of unclear origin, we diagnosed lymphedema in 47% and venous insufficiency in 21%, the latter confirmed by a venous duplex scan. Accordingly, lymphatic insufficiency, venous insufficiency or both were diagnosed in all of these patients (68%), by using both the duplex scan and LAS. Although these tests did not prove the abnormality, they indicated that 24% of the patients suffered from some type of “functional” venous insufficiency because they all had skin lesions that were obviously affected by the venous congestion. Therefore, 45% of the patients probably had venous insufficiency.

There is still no clear delineation for “functional” venous insufficiency. In chronic venous insufficiency (CVI), which is generally considered chronic venous disease of C4 or greater,^{8, 9)} not only calf muscle pump impairment,¹⁰⁾ but also reduced ankle range of motion¹¹⁾ and gait abnormality¹²⁾ are all thought to be related to the disease process. Thus, it is likely that these conditions can cause venous edema, which could be classified as C3EnAnPn. Interestingly, patients with ankle or knee problems, even when they can walk independently, often suffer leg edema. Many such patients are frustrated to be told by physicians that they are fine. In fact, their symptoms can be improved dramatically by compression and physical therapy. It is also true that if joint problems are temporary, such as those caused by trauma or inflammation, the leg edema will disappear. Many patients with lymphedema might have this “functional” venous insufficiency, since their ambulation is impaired to some degree; however, there is no way to access this condition objectively at present.

In Japan, the routine use of LAS to help in the diagnosis of lymphedema is still controversial, mainly because it is costly and not covered by insurance. However, the Consensus Document of the International Society of Lymphology¹³⁾ describes that “a low output failure of the lymphvascular system” is the central mechanism of lymphedema in its purest form. The only widespread and currently available diagnostic tool to show this is LAS, which means that definite diagnosis of lymphedema can only be made by LAS at this stage. We have had patients referred to us for the management of lymphedema without clear evidence of this diagnosis. Some had already been treated with invasive methods, such as epidural or lumbar sympathetic ganglion block, before LAS eventually found that they were simply fat with normal lymphatic function.

Some skin ultrasound findings, such as thickened dermis, thickened and high-echoic subcutis, or reduced echo-contrast between the dermis and subcuticular fat,^14–16) are indicative of lymphedema. Yet, as these are not specific findings of lymphedema, only experienced lymphologists should make a definitive diagnosis based on these observations. Furthermore, these findings might not be evident in the early stages of the disease, strongly suggesting that LAS should be performed whenever we suspect lymphedema.

The leg mobility of patients with lymphedema is impaired by heaviness and stiffness of the lower extremities; however, their impact on the muscle/ joint pump in the venous system, subsequently effecting venous congestion cannot be determined, though they do represent worsening of the edema. Many patients suffered lumbago and hip or knee problems, which again affect venous pump function in the legs. Moreover, most patients were on medications that can cause edema. Because leg edema is affected by so many factors, legs do not always manifest typical signs but rather complicated signs, such as lymphedema plus venous congestion, of varying degree, as seen in our series. Since there are no diagnostic guidelines for lymphedema defined by objective findings or parameters, diagnosing “lymphedema” in this situation is not easy for most physicians, even experts. We do not have to make a diagnosis; however, we are required to confirm the lymphatic insufficiency causing the lymph congestion in order to manage and treat lymphedema. For this purpose, LAS is necessary and sufficient. Similarly, for chronic venous insufficiency, venous obstruction or reflux seen on the duplex scan may not be the main cause of edema, but it is apparently affecting the venous return. Specific skin manifestations such as pigmentation, lipodermatosclerosis, characteristic dermatitis, or skin ulcers all indicate venous congestion, even without abnormalities on duplex scans. Treatments, including complex physical therapy, are indicated by these findings.

As a matter of course, any type of edema should be investigated thoroughly and treated individually, although sometimes this is impossible. For example, specific medications such as insulin, anti-platelet drugs, or anti-psychotics may cause edema, though the patients cannot stop taking their drugs nor have their treatments changed. For them, the leg edema is not necessarily cured completely; however, we can reduce the edema, depending on the complaint of the patient. Edema is caused by various factors, demonstrating that we must treat the manageable factors and leave the untreatable factors alone. From this viewpoint, complex physical therapy (CPT)¹⁾ could be the first-line treatment for any type of edema because of its safety and effectiveness.

For lymphedema, CPT helps to reduce lymphatic congestion through a combination of physical therapies. One such therapy, compression therapy improves venous return, by supporting muscle/joint pumps in the legs, and reduces tissue fluid, by increasing the interstitial pressure. These additional effects are favorable for any type of edema, regardless of their cause. Furthermore, there are few complications if the therapy is done properly. This treatment method is gaining in popularity, and more therapists are being trained in the method; however, very few physicians prescribe CPT.

The use of both venous duplex ultrasound and LAS also aids in establishing an appropriate treatment strategy. When venous insufficiency is found, treatment basically consists of below-knee multi-layered bandage, physical and occupational therapy to improve range of motion of the ankle, and calf-muscle training. Severe venous problems such as varicose veins or incompetent perforating veins should be corrected surgically.⁹⁾ On the other hand, when lymphatic insufficiency is found, complex physical therapy, including lymphedema multi-layered bandage, manual lymph drainage, exercise, skin care, and self-care, should be the treatment of choice. Lymphatic surgery and other supplemental treatments can be added if indicated.^{1, 13)} For complex cases, both treatments may be indicated, but should be balanced depending on the patient's compliance, since reduced venous congestion also unloads lymphatic system. For instance, we diagnosed secondary lymphedema and varicose veins in a patient who had been admitted for “cellulitis” every 3 months; yet, this patient did not suffer cellulitis after varicose vein surgery.

Conclusion

By using both venous duplex ultrasound and LAS, we could make a definite diagnosis in 68% of patients with leg edema of unknown cause. Lymphedema was confirmed in about half of these patients, whereas the other half had some sort of venous edema, a quarter of which seemed to be due to “functional” venous insufficiency. Further delineation of this “functional” venous insufficiency and guidelines for diagnosis are needed. The use of these two diagnostic tools to verify the existence of venous and lymphatic problems also proved helpful to establish treatment strategies. Thus, we strongly recommend the use of both venous ultrasound and LAS to assist in establishing the diagnosis of leg edema of unclear origin.