| disease | Lymphedema |
Lymphedema refers to the obstruction of lymphatic fluid reflux in certain parts of the body, leading to the accumulation of soft tissue fluid. After repeated infections, subcutaneous fibrous connective tissue proliferates, and fat hardens. If it occurs in a limb, the limb thickens. In the late stage (third stage), the skin thickens, becomes rough, and toughens like elephant hide, also known as "elephant hide swelling."
bubble_chart Etiology
The classification of lymphatic edema diseases is diverse, encompassing both disease causes and clinical types, primarily divided into primary and secondary categories. Primary lymphatic edema is mostly caused by congenital developmental abnormalities such as lymphatic vessel dilation, valve membrane insufficiency, or absence. Based on lymphangiography, primary lymphatic edema can be classified as follows: ① Lymphatic hypoplasia, accompanied by the absence of subcutaneous lymphatics; ② Lymphatic hypoplasia, with small and few lymph nodes and lymphatic vessels; ③ Lymphatic hyperplasia, with large and numerous lymph nodes and lymphatic vessels, sometimes twisted and varicose. Among these, lymphatic hypoplasia is very rare and commonly seen in congenital lymphatic edema. Hypoplasia is the most common type. Both simple and accompanying lymphatic edema are congenital. Early-onset lymphatic edema is more common in adolescent females or young women, with symptoms worsening during menstruation, leading to speculation that the disease cause may be related to endocrine disorders, accounting for 85–90% of primary lymphatic edema. Cases that develop after the age of 35 are referred to as late-onset lymphatic edema. Secondary lymphatic edema is mostly caused by lymphatic vessel obstruction. The most common types domestically are filariasis-induced lymphatic edema and streptococcal infection-induced lymphatic edema. Upper limb lymphatic edema following radical mastectomy for breast carcinoma is also not uncommon.
Although Herophilos and Aristotle observed the lymphatic system as early as the third and fourth centuries, and extensive experimental research has been conducted in modern times, the exact pathogenesis of lymphatic edema remains unclear.Classification:
(1) Primary lymphatic edema
1. Congenital: Simple
Hereditary (Milroy disease)
2. Early-onset
(2) Secondary lymphatic edema
1. Infectious: Chinese Taxillus Herb worms, bacteria, fungi, etc.
2. Traumatic: Surgery, radiotherapy, burns, etc.
3. Malignant tumor-related: Primary tumors, secondary tumors
4. Others: Systemic diseases, pregnancy, etc.
bubble_chart Pathological Changes
Lymph is the interstitial fluid in the spaces between cells, which flows back into the veins through lymphatic vessels. The lymphatic circulation is also a part of the human body's physiological functional circulation. If the lymphatic system is congenitally underdeveloped or becomes obstructed or damaged due to certain reasons, the distal lymphatic return will be impaired, leading to an abnormal increase in lymphatic fluid in the tissue spaces. If this occurs in a limb, the affected limb will uniformly thicken. Initially, the skin remains smooth and soft, and elevating the affected limb can significantly reduce the edema. Since the lymphatic fluid in the abdominal mass is rich in proteins—up to 5.8 g/dl (normal: 0.72 g/dl)—long-term stimulation causes abnormal proliferation of connective tissue, replacing adipose tissue with large amounts of fibrous tissue. The skin and subcutaneous tissues become extremely thickened, with keratinized and rough surfaces that do not show indentation upon pressure, leading to the formation of wart-like growths and the typical "elephant hide" appearance. Infections increase inflammatory exudate, stimulating excessive connective tissue proliferation, damaging more lymphatic vessels, worsening lymphatic fluid retention, and increasing the risk of secondary infections, creating a vicious cycle that progressively aggravates lymphatic edema.
bubble_chart Clinical ManifestationsAccording to the above classification of disease causes, their respective clinical characteristics are described as follows:
(1) Congenital lymphedema Divided into two types:
1. Simple type No familial or hereditary factors are involved in the onset. The incidence accounts for 12% of primary lymphedema. There is localized or diffuse swelling of one limb at birth, which is painless and without ulceration. Infection is rare, and the general condition is good. It mostly occurs in the lower limbs.
2. Hereditary type Also known as Milroy disease, it is relatively rare. Multiple members of the same family are affected, and the condition manifests at birth, usually involving one lower limb.
(2) Early-onset lymphedema More common in females, with a male-to-female ratio of 1:3. The age of onset ranges from 9 to 35 years, and 70% of cases are unilateral. Grade I swelling of the ankle typically appears without obvious triggers and worsens with standing, activity, menstruation, and warm weather. Elevating the affected limb can temporarily reduce the edema. The condition gradually progresses and spreads to the calf but generally does not extend beyond the knee joint. In the late stage (third stage), it may present as a typical "swollen foot wind wilting," but ulceration and secondary infections are rare.
(3) Infectious lymphedema Includes infections caused by bacteria, fungi, filariasis, etc. Fissures or blisters on the toes are the most common entry points for pathogens. Other pathways include secondary infections from varicose veins with ulcers, as well as local injuries or infections. Additionally, pelvic lymphadenitis due to pelvic inflammation in females can obstruct lymphatic drainage, leading to lymphedema in the affected limb. Streptococcus is the most common pathogen in secondary infections. Clinically, it is characterized by recurrent acute cellulitis and lymphangitis, with severe systemic symptoms such as chills, high fever, nausea, and vomiting, along with swollen and tender inguinal lymph nodes. Systemic symptoms subside quickly with anti-inflammatory treatment, but local resolution is slower and prone to recurrence. Each episode exacerbates limb swelling, eventually leading to rough skin and wart-like growths, with a few cases progressing to chronic ulcers.
Tinea pedis itself or secondary infections can also cause lymphedema, usually limited to the foot and dorsum. Severe fungal infections often precede acute cellulitis and lymphangitis. Controlling fungal infections is one of the effective measures to prevent lymphedema.Filariasis is a common cause of lower limb lymphedema in the southeastern coastal regions of China, with an incidence of 4–7% and a higher prevalence in males. In the initial stage (first stage), filariasis infection presents with varying degrees of fever and local distending pain. Repeated infections lead to narrowing, occlusion, and destruction of local lymphatic vessels, obstructing lymphatic drainage in the distal skin and subcutaneous tissues, resulting in lymphedema. Local lesions like tinea pedis or recurrent erysipelas-like episodes create a vicious cycle of obstructed lymphatic drainage and infection, eventually leading to the classic "swollen foot wind wilting." Scrotal lymphedema is also common, and in advanced stages, the scrotum may become extremely enlarged, which is a notable feature of filarial lymphedema.
(4) Traumatic lymphedema Mainly includes postoperative lymphedema and post-radiotherapy lymphedema.
1. Postoperative lymphedema Often occurs after lymph node dissection, particularly in the upper limb following radical mastectomy for breast cancer. Extensive lymph node dissection obstructs distal lymphatic flow, and lymphatic fluid stimulates tissue fibrosis, progressively worsening the swelling. The timing of postoperative lymphedema varies widely; it may begin with grade I swelling in the proximal limb upon initial activity or develop weeks or even months after surgery.
2. Post-radiotherapy lymphedema Deep X-ray and radium therapy cause local tissue fibrosis and lymphatic vessel occlusion, leading to lymphedema.
(5) Malignant neoplastic lymphedema Both primary and secondary malignant tumors of the lymphatic system can obstruct lymphatic vessels, leading to lymphedema. The former is seen in Hodgkin's disease, lymphoma, Kaposi's multiple hemorrhagic sarcoma, and lymphangiosarcoma. Although lymphangiosarcoma is rare, it is often the result of long-term malignant transformation of lymphedema. It mostly occurs in patients who develop lymphedema in the limbs after radical mastectomy for breast carcinoma, typically manifesting around 10 years post-surgery. Initially, red or purple spots appear on the skin, which are multiple and later coalesce into ulcerative masses. After onset, limb lymphedema becomes more severe. A timely biopsy should be performed. Once diagnosed, amputation is required.
Secondary lymphatic system lesions are metastatic cases of cancers in the breast, uterine cervix, labia, prostate, bladder, testis, skin, and internal skeleton. Sometimes the primary lesion is small and difficult to detect, with clinical manifestations including chronic, episodic, painless, and progressive lymphatic edema. Therefore, for unexplained lymphatic edema, the possibility of tumors should be considered, and lymph node biopsy may be necessary for definitive diagnosis.
Additionally, pregnancy and various systemic diseases such as pneumonia, common cold, cold-damage disease, etc., can also lead to recurrent cellulitis and lymphangitis, accompanied by venous thrombosis and lymphatic obstruction, resulting in lymphatic edema.
bubble_chart Auxiliary Examination
(1) Diagnostic Puncture Tissue Fluid Analysis Analysis of subcutaneous edema tissue fluid aids in the differential diagnosis of challenging cases. Lymphatic edema fluid typically has a high protein content, usually ranging from 1.0 to 5.5 g/dl, whereas edema fluid from simple venous stasis, heart failure, or hypoalbuminemia has a protein content of 0.1 to 0.9 g/dl. This test is commonly used for chronic, thickened swollen limbs and can be performed simply and conveniently with just a syringe and a fine needle. However, it does not provide information about the location or functional status of lymphatic vessel lesions. It is a rough diagnostic method.
(2) Lymphangiography Lymphangiography involves puncturing a lymphatic vessel to inject a contrast agent and then taking radiographs to visualize the morphology of the lymphatic system. It is a specific auxiliary examination for lymphatic edema.
1. Indications
⑴ Differentiation between lymphatic edema and venous edema.
⑵ Differentiation between primary lymphatic edema and secondary lymphatic edema.
⑶ Candidates for lymphovenous anastomosis.
2. Lymphangiography Method Currently, the direct lymphatic vessel puncture and contrast injection method is predominantly used. First, 0.25–0.5 ml of Evans blue is injected subcutaneously at the level of the 1st to 4th metatarsal bones on the dorsum of the foot. After 3–5 minutes, thin blue superficial lymphatic vessels become visible. Under local anesthesia, the skin is incised to expose the superficial lymphatic vessels. Fine sutures are looped around the proximal and distal ends of the vessel, temporarily blocking the proximal end to retain lymph fluid. A 27–30 gauge needle is used to puncture the lymphatic vessel, followed by injecting a small amount of 1% procaine to confirm intraluminal placement and rule out fistula formation. The needle is then secured and connected to a syringe via a plastic tube. Ethiodol (12 ml) is injected at a uniform rate of 0.1–0.2 ml/minute. After injecting 2 ml, radiographs of the ankle and pelvis are taken to check for contrast leakage and to exclude accidental venous injection. Upon completion, the needle is removed, and the lymphatic vessel is ligated to prevent lymphatic fistula formation. The skin is sutured. Radiographs include anteroposterior views of the lower leg and thigh, as well as anteroposterior, oblique, or lateral views from the groin to the first lumbar vertebra.
3. Abnormal Findings in Lymphangiography
⑴ Primary lymphatic edema: Absence or insufficiency of lymphatic valve membranes, with dilated and tortuous lymphatic vessels.
⑵ Secondary lymphatic edema: Mid-segment lymphatic vessel obstruction, with dilated and tortuous distal lymphatic vessels, increased in number and irregular in shape. Metastatic lymph nodes may show filling defects with moth-eaten margins.
4. Complications
⑴ Incision infection, lymphatic fistula formation.
⑵ Systemic reactions: Fever, nausea, vomiting; in rare cases, peripheral circulatory collapse may occur due to contrast agent allergy.
⑶ Reactive inflammation of local lymphatic vessels, exacerbating lymphatic edema.
⑷ Pulmonary embolism: The contrast agent may enter veins through anastomotic collaterals under increased pressure, causing pulmonary embolism, with an incidence rate of 2–10%. Fatal cases due to pulmonary embolism have been reported in the literature. {|114|}
(3) Isotope Lymphangiography Since X-ray lymphangiography cannot provide quantitative dynamic data on the function of the lymphatic system or a straightforward overview of lymphatic drainage from different limb regions, a valuable static lymphatic scintigraphy (radionuclide imaging) has been developed. A 0.25ml (75MBq) injection of 99m-technetium sulfide colloid is administered into the subcutaneous tissue of the second interdigital space of both feet. A gamma camera is positioned directly over the patient's lower abdomen and inguinal region, and static images are scanned at 1/2, 1, 2, and 3 hours. The amount of isotope uptake in the iliac and inguinal lymph nodes is then calculated separately. Studies using isotope imaging to assess lymphatic function in chronic lymphedema indicate that the degree of reduced lymphatic drainage in the affected limb correlates with the severity of lymphedema. In severe lymphedema, the isotope uptake rate is nearly 0, whereas in static venous edema, the absorption percentage of lymphatic drainage increases significantly. Therefore, this method can differentiate between lymphatic edema and venous edema, with a diagnostic sensitivity of 97% and specificity of 100% for lymphedema. Compared to X-ray lymphangiography, radionuclide imaging is simpler to perform and provides clearer diagnostic results. However, it cannot anatomically localize lymphatic vessels and lymph nodes. If lymphatic surgery is being considered, X-ray lymphangiography remains the preferred method.
In addition, the newly developed non-invasive vascular detection technology also helps differentiate between venous edema and lymphatic edema. As an outpatient screening method, it is both simple and convenient.
1. History of filariasis infection or recurrent erysipelas, or history of lymph node dissection and radiotherapy in the axillary or groin area.
2. In the early stage, the affected limb swells, which can be relieved by elevation. In the advanced stage, the limb is significantly enlarged, with a keratinized and rough surface, presenting as an elephantiasis-like swelling. A few cases may exhibit skin fissures, ulcers, or wart-like growths.
3. Microfilariae may be detected in peripheral blood tests of filariasis patients. Lymphangiography can determine the development or obstruction of lymphatic vessels.
bubble_chart Treatment Measures
Lymphatic edema has different treatment principles depending on the stage of the disease. In the early stage, the goal is to eliminate the retention of lymphatic fluid and prevent its recurrence, while in the advanced stage, the focus shifts to surgical removal of irreversibly damaged tissues or shunt procedures to treat localized lymphatic obstruction.
(1) Acute lymphatic edema is primarily managed with non-surgical treatments.
1. Postural drainage: Allowing the limb to hang downward exacerbates lymphatic stasis in the interstitial spaces. Elevating the affected limb by 30–40 cm utilizes gravity to promote lymphatic return and reduce edema. This method is simple and effective but not long-lasting, as edema worsens again when the limb is lowered.
2. Compression bandaging: Building on postural drainage, elastic stockings or bandages are applied to the elevated limb to compress the interstitial spaces and aid lymphatic return. The tightness of the bandage should be appropriate. Intermittent compression pumps can also be used multiple times for extended periods, showing some efficacy in improving edema. Literature reports that abroad, a more advanced and effective pneumatic device called the lymha-press is currently used. This device consists of 9–12 individually inflatable segments, with pressure applied sequentially from the distal to the proximal limb, completing one cycle in 25 seconds. Compared to simpler compression devices (which take about 100 seconds per cycle), the lymha-press significantly shortens the inflation time while generating higher pressures (15.6–20.8 kPa or 120–160 mmHg), proving more effective than surgery or simple elastic stockings in reducing swelling. However, its use is more complex and does not reduce protein content in the interstitial spaces, making it suitable only for short-term treatment during the acute phase or preoperative preparation.
3. Sodium restriction and diuretics: During the acute phase, sodium chloride intake should be moderately restricted (generally 1–2 g/day) to reduce sodium and water retention in tissues. Concurrently, appropriate diuretics can accelerate the excretion of water and sodium. Hydrochlorothiazide (25 mg three times daily) may be used with potassium supplementation, and discontinued once the condition stabilizes.
4. Infection prevention: Antifungal ointments and powders, along with keeping the toes dry, are the most effective methods to prevent and control fungal infections. Bacterial infections under the toenails are also common, so regular nail trimming and cleaning are essential to minimize bacterial entry. For systemic symptoms of streptococcal infection, penicillin and other medications should be used alongside bed rest to actively control the infection. In advanced lymphatic edema complicated by skin rhagades, topical ointments can be applied to protect and lubricate the skin.
Additionally, various vaccines, milk, and heterologous protein injections have long been used as anti-infection therapies. These methods enhance the body's defense mechanisms. Foreign scholars have demonstrated that injecting a triple vaccine for cold-damage disease increases lymphocytes in the efferent lymphatic vessels and elevates gamma globulin levels in the blood, potentially preventing permanent lymphatic obstruction. Some authors speculate that heterologous proteins may act through the pituitary and adrenal glands.
(2) Chronic lymphatic edema includes non-surgical treatments like烘绷 therapy and various surgical interventions.
1. Baking Bandage Therapy Baking bandage therapy is a treatment method developed from the heritage of traditional Chinese medicine. Its therapeutic principle involves using continuous radiant heat to dilate the blood vessels in the skin of the affected limb, induce profuse sweating, and facilitate the return of interstitial fluid into the bloodstream, thereby improving lymphatic circulation. This therapy is suitable for cases of lymphedema where severe skin hyperplasia has not yet occurred. There are two methods: electric radiant heat therapy and heating with a baking oven. The temperature is controlled between 80–100°C, administered once daily for one hour per session, with 20 sessions constituting one treatment course. A 1–2 week interval is recommended between courses. After each treatment, an elastic bandage should be applied for compression. Clinical observations indicate that after 1–2 courses of treatment, the affected limb's tissues become softer, the limb gradually reduces in size, and notably, the frequency of erysipelas-like episodes significantly decreases or ceases altogether.
2. Surgical Treatment Most cases of lymphedema do not require surgical intervention. Approximately 15% of primary lymphedema patients eventually undergo lower limb plastic surgery. Current surgical methods, except for amputation, cannot cure lymphedema but can significantly alleviate symptoms.
(1) Surgical Indications: ① Functional impairment of the limb: Due to heaviness, fatigue, and restricted joint movement. ② Severe swelling accompanied by pain. ③ Recurrent cellulitis and lymphangitis unresponsive to medical treatment. ④ Lymphatic fleshy tumor: A fatal complication of long-term lymphedema. ⑤ Cosmetic concerns: Most primary lymphedema patients are young women. Surgery may be considered for those with significant swelling and cosmetic demands, but the primary goal should be functional improvement, with aesthetics as a secondary consideration. Otherwise, the results may be unsatisfactory.
Preoperative Preparation and Postoperative Management:
(2) Preoperative Preparation Plays a crucial role in surgical outcomes. Measures include: ① Bed rest with limb elevation: Minimize limb edema as much as possible. Methods include leg elevation, limb suspension, and bone traction, with a recommended elevation angle of 60º. ② Infection control: For recurrent acute cellulitis and lymphangitis, sensitive antibiotics should be administered intravenously or intramuscularly before and during surgery to reduce postoperative flap infection risks. ③ Skin cleansing: Aim to heal ulcers or control local infections. ④ Ensuring postoperative drainage: The separated rough surfaces may have continuous capillary bleeding. Negative-pressure drainage must be placed to prevent blood or fluid accumulation under the flap, reduce factors affecting flap blood supply, and avoid flap necrosis, infection, and surgical failure. ⑤ Continued limb elevation postoperatively to reduce edema and promote venous and lymphatic return.
(3) Surgical Classification: Lymphedema surgery can be divided into two categories: ① Extensive excision of diseased tissue. ② Lymphatic flow reconstruction. Experimental and clinical evidence suggests that the partial or substantial benefits of the latter are actually achieved based on the extensive removal of diseased tissue. Simply reconstructing lymphatic flow, despite meticulous surgical techniques, yields minimal therapeutic effects. Since secondary lymphedema often involves intact lymphatic systems proximal and distal to the obstruction point, surgical reconstruction of local lymphatic flow can achieve good results. In contrast, most primary lymphedema cases involve hypoplastic lymphatic vessels proximal and distal to the affected area, making it unrealistic to expect significant symptom improvement from lymphatic flow reconstruction alone.
In the early stages, due to mild changes in the skin and subcutaneous tissues, it should be differentiated from other diseases:
1. Venous edema Commonly seen in deep vein thrombosis of the lower limbs, it presents with sudden unilateral limb swelling, accompanied by cyanosis, significant tenderness in the gastrocnemius muscle and femoral triangle, and prominent superficial veins. Dorsal foot edema is not obvious. In contrast, lymphedema develops more slowly, with swelling predominantly in the dorsal foot and ankle.
2. Angioneurotic edema Edema occurs due to external allergic stimuli, with rapid onset and resolution, characterized by intermittent episodes. Lymphedema, however, tends to worsen gradually.
3. Systemic diseases Hypoproteinemia, heart failure, nephropathy, cirrhosis, and myxedema can all cause lower limb edema. It is usually bilateral and symmetrical, accompanied by clinical manifestations of the respective primary diseases. Differentiation can typically be made through detailed medical history, careful physical examination, and necessary laboratory tests.
4. Congenital arteriovenous fistula Congenital arteriovenous fistula may present with limb edema, but the affected limb is generally longer and larger in circumference than the healthy side, with increased skin temperature, superficial varicose veins, and vascular murmurs audible in localized areas. The oxygen content of peripheral venous blood is close to that of arterial blood. These are its unique characteristics.
5. Lipoma A few cases of extensive lipomas or adipose tissue hyperplasia may be confused with lymphedema. However, lipomas mostly exhibit localized growth, progress slowly, and the subcutaneous tissue is soft without edema. If necessary, soft tissue X-ray mammography can aid in definitive diagnosis.
