I. Overview
Lymphedema is a soft tissue fluid proliferation, fat sclerosis and thickening of subcutaneous fibrous connective tissue after repeated infections on the body surface caused by obstruction of lymphatic flow in certain parts of the body, and in the case of limbs, thickening, roughness and toughness of the skin like elephant skin in the later stage, also called “elephantiasis”.
Etiology
The etiology of lymphedema is classified into many categories, taking into account the etiology and clinical type, mainly divided into two categories: primary and secondary. Primary lymphedema is mostly caused by congenital dysplasia such as dilated lymphatic vessels, valvular insufficiency, or orthoplasia. According to lymphangiography, primary lymphedema can be classified as follows.
(1) Lymphatic dysplasia with subcutaneous lymphatic agenesis;
② Hypolymphatic development with small lymph nodes and lymphatic vessels;
(3) Lymphatic hyperplasia with large and numerous lymph nodes and lymphatic vessels, sometimes with distortion and varicosity.
Among them, lymphatic hypoplasia is very rare and is commonly associated with congenital lymphedema. Hypoplasia is the most common type. Both solitary and command lymphedema are congenital. Early-onset lymphedema is most often seen in adolescent women or young women, with symptoms worsening during menstruation, so the cause is presumed to be related to endocrine disorders, accounting for 85-90% of primary lymphedema. Secondary lymphedema is mostly caused by obstruction of lymphatic vessels. The most common ones in China are filariasis lymphedema and streptococcal infection lymphedema. Upper limb lymphedema is also not uncommon after radical breast cancer surgery.
Although Herophilos and Aristotle observed the lymphatic system as early as the third and fourth centuries, and a lot of experimental studies have been done in recent times, the exact pathogenesis of lymphedema is not clear.
Classification.
(A) Primary lymphedema
1. Congenital: simple
Hereditary (milroy disease)
2, early onset
(II) Secondary lymphedema
1.Infectious: parasites, bacteria, fungi, etc.
2.Injury: surgery, radiotherapy, burns, etc.
3.Malignant tumor: primary tumor, secondary tumor
4.Other: systemic diseases, pregnancy, etc.
According to the WHO recommended lymphedema staging method, limb lymphedema is divided into stage VII.
Characteristics of stage Ⅰ lymphedema: swelling can subside after bed rest at night, and acute bacterial infection rarely occurs or unpleasant odor is rare.
Characteristics of stage II lymphedema: swelling cannot subside after nighttime bed rest, with occasional acute bacterial infection, skin breakage or mild odor.
Characteristics of stage III lymphedema: swelling that does not subside after nighttime bed rest, one or more skin folds on the swollen skin, occasional acute bacterial infection, often skin breakdown and a distinct odor.
Features of stage IV lymphedema: the swelling does not subside after nighttime bed rest and is accompanied by a verrucous protrusion. The swollen skin is covered with uneven hard nodules or verrucous nodules. Some patients have occasional acute bacterial infections, often with skin breakdown and foul odor.
Features of stage V lymphedema: the swelling does not subside after nighttime bed rest and is accompanied by deep skin folds. Occasional or frequent acute bacterial infections occur, and most patients have skin breakdown and odor between the toes or deep skin folds. The swelling may extend above the knee.
Characteristics of stage VI lymphedema: The swelling does not subside after nighttime bed rest and is accompanied by mossy feet. There are many very small, clustered long or round nodules on the foot (especially the toes), forming a mossy manifestation called a mossy foot. There is an acute bacterial infection and almost all patients have skin breakdown and foul odor between the toes, often accompanied by skin fissures.
Features of stage VII lymphedema: swelling that does not subside after nighttime bed rest and is accompanied by impairment of the patient’s self-care, often with acute bacterial infection, huge deep folds of skin on the lower or upper extremities, persistent skin breakdown and a distinct odor within the deep folds and between the toes. In most patients, the swelling may extend above the knee. Patients at this stage are unable to perform daily activities independently.
III. Pathological changes
Lymph is the tissue fluid in the intercellular space that flows back into the veins via the lymphatic vessels. The lymphatic circulation is also a physiological and functional body circulation of the body. If the lymphatic system is congenitally underdeveloped or occluded or destroyed for some reason, the distal lymphatic flow is impaired and the lymphatic fluid in the interstitial space of the tissue is abnormally increased. If it occurs in the limb, the affected limb is uniformly thickened, the skin is initially smooth and soft, and the edema can be significantly reduced by elevating the affected limb. As the accumulated lymphatic fluid is rich in protein, it can be as high as 5.8g/dl, [normal 0.72g/dl] long-term stimulation causes abnormal proliferation of connective tissue, and fatty tissue is replaced by a large amount of fibrous tissue.
The skin and subcutaneous tissues are extremely thickened, the skin surface is keratinized and rough, no indentation occurs after finger pressure, and wart-like growths appear, forming a typical “elephantiasis”. Infection increases inflammatory exudate, stimulates a large number of connective tissue proliferation, destroys more lymphatic vessels, aggravates lymphatic fluid retention, increases the chance of secondary infection, and forms a vicious circle, resulting in increasing aggravation of lymphedema.
IV. Clinical manifestations
According to the above etiological classification, their respective clinical characteristics are described as follows.
(I) Congenital lymphedema There are two types of congenital lymphedema.
(1) Simple There are no family or genetic factors in the onset of the disease. The incidence accounts for 12% of primary lymphedema. There is limited or diffuse swelling of one limb after birth, no pain, no ulceration, rarely complicated by infection, and generally good condition, mostly in the lower limbs.
2. Hereditary Also known as Milroy’s disease, it is relatively rare. Multiple people in the same family have the disease, i.e., it develops after birth, and mostly involves one lower extremity.
(B) Early-onset lymphedema is common in women, with a male to female ratio of 1:3, with an age of onset of 9 to 35 and 70% unilateral. Mild swelling of the foot and ankle generally occurs without obvious inducements and is aggravated by standing, activity, menstruation and warm weather. The edema of the affected limb may be temporarily reduced by finger height. The lesion gradually worsens and spreads to the lower leg, but usually does not exceed the knee joint. In the later stage, it may appear as a typical “elephant skin leg”, but it is rarely complicated by ulceration and secondary infection.
(C) Infectious lymphedema includes bacterial, fungal, filarial and other infections. Toe skin cracks or blisters are the most common route of invasion of pathogenic bacteria, followed by varicose veins of the lower extremities with ulcers and other local injuries or infections. In addition, pelvic lymphadenitis caused by pelvic inflammatory disease in women, which can block lymphatic return to the lower extremities causing lymphatic dysplasia in the affected extremities, has also been reported.
Streptococcus is the most common pathogenic organism for secondary infections. The clinical picture is characterized by recurrent acute cellulitis and acute lymphangitis, with severe systemic symptoms, chills, high fever with nausea and vomiting, and localized sulcular lymph node enlargement with pressure pain. With anti-inflammatory and symptomatic treatment, the systemic symptoms subside quickly, but the local lesions resolve slowly and are prone to recurrence. The swelling of the lower extremities increases with each attack, and eventually the skin becomes rough with warty growths, and in a few cases, chronic ulcers may develop.
Tinea pedis itself or secondary infections also cause lymphedema, which is usually confined to the foot and dorsum of the foot, and severe fungal infections are often a precursor to acute cellulitis and acute lymphangitis. Control of fungal infections is one of the effective measures to prevent lymphedema.
Filarial sense is a common cause of lower limb lymphedema in the southeastern coastal region of China. The incidence is 4-7%, and it is more common in men. The initial stage of filarial infection has different degrees of fever and local swelling and pain. Repeated filarial infections narrow, occlude, and destroy local lymphatic vessels in the lower extremities, blocking the lymphatic fluid return to the distal skin and subcutaneous tissues to which they belong, and causing lymphedema. Local lesions such as tinea pedis or secondary recurrent episodes of dermatophytosis make lymphatic drainage obstruction and infection mutually causal, forming a vicious circle and eventually becoming a typical “elephant skin leg”. Its flash, scrotal lymphedema is more than rare, and the advanced stage can lead to extreme enlargement of the scrotum. This is also a feature of filarial infectious lymphedema.
(D) Injurious lymphedema Mainly divided into post-surgical lymphedema and post-radiotherapy lymphedema.
1. Post-surgical lymphedema often occurs after lymph node dissection, and lymphedema of one upper limb caused by radical breast cancer surgery is especially common. After extensive lymph node dissection, the distal lymph is obstructed and the lymphatic fluid stimulates tissue fibrosis, which makes the swelling increase continuously. The time of lymphedema after surgery varies greatly, and generally there is mild swelling of the proximal limb when the limb starts to move after surgery, but it can also occur in the weeks or even months after surgery.
2.Lymphedema after radiotherapy Deep X-ray and radium ingot therapy cause local tissue fibrosis and lymphatic vessel occlusion resulting in lymphedema.
(E) Malignant lymphedema Both primary and secondary malignant tumors of the lymphatic system can block lymphatic vessels and produce lymphedema. The former is seen in Hodgkin’s disease, lymphosarcoma, Kaposi’s multiple hemorrhagic sarcoma, and lymphangioleiomyosarcoma. Although lymphangioleiomyosarcoma is rare, it is the result of malignant transformation of long-term lymphedema. It occurs mostly in patients with lymphedema in the limbs after radical breast cancer surgery, and usually develops 10 years after surgery. The lymphedema of the limb is more severe after the onset of the disease. A biopsy should be performed promptly. Amputation of the limb is required after the diagnosis is clear.
Secondary lymphatic system lesions are cases of metastases from carcinomas of breast, cervix, labia, prostate, bladder, testis, skin, endoskeleton, etc.. Sometimes the primary foci are small and not easily detected, and the clinical presentation is chronic transitory, painless, progressive lymphedema. Therefore, for lymphedema of unknown cause, we should be alert to the possibility of tumor, and if necessary, lymph node biopsy should be performed to clarify the diagnosis.
In addition, pregnancy and many systemic diseases such as pneumonia, influenza and typhoid can also lead to recurrent cellulitis and lymphangitis, as well as lymphedema caused by venous thrombosis and lymphovascular obstruction.
V. Auxiliary examination
(a) Diagnostic puncture tissue fluid analysis The analysis of subcutaneous edema tissue fluid can help in the differential diagnosis of difficult cases. The protein content of lymphedema fluid is usually very high, usually in the range of 1.0-5.5 g/dl, while the protein content of edematous tissue fluid in simple venous depression, heart failure or hypoproteinemia is in the range of 0.1-0.9 g/dl. The examination is usually used for chronic gross swollen limbs and can be performed with only a syringe and fine needle, which is a simple and convenient method. However, the lesion site and function of the lymphatic vessels cannot be understood. It is a crude diagnostic method.
(B) Lymphadenography Lymphatic duct puncture with contrast injection and radiography to show the morphology of the lymphatic system is an examination method, and is a specific auxiliary examination for lymphedema.
1. Indications
(1) To distinguish lymphedema from venous edema.
(2) To distinguish primary lymphedema from secondary lymphedema.
(3) To perform lymphatic-venous anastomosis.
2.Lymphangiography method
At present, direct lymphatic duct puncture injection imaging method is mostly used. Firstly, subcutaneous injection of Evansylan.25~0.5ml at the level of the 1st to 4th metatarsal on the dorsal side of the foot will be visible in 3~5 minutes as a thin blue strip of superficial lymphatic vessels. The superficial lymphatic vessels were separated by cutting the skin under local anesthesia, and a thin wire was wrapped around each of the proximal and distal ends to temporarily block the proximal end so that the lymphatic fluid was retained, and the lymphatic vessels were punctured with a 27-30 gauge needle, then a small amount of 1% procaine was injected to confirm that it was in the lumen and did not leak, and the needle was fixed and connected to the syringe through a plastic tube and injected at a uniform rate of 0.1-0.2 ml/min. Ethiodol 12ml (ethyl iodide oil). After injection of 2 ml, radiographs were taken at the ankle and pelvis to identify any extravasation of the contrast agent and to discard any misinjection into the vein. After the injection, the needle was removed, the lymphatic vessels were ligated to prevent lymphatic leakage, and the skin was sutured.
The radiographs include: anterior-posterior position of the lower leg, anterior-posterior position of the thigh, anterior-posterior, oblique or lateral position from the groin to the first lumbar vertebra.
3. Abnormal manifestations of lymphangiography
(1) Primary lymphedema: lymphatic vessel valves are absent or incompetent, and lymphatic vessels are dilated and tortuous.
(2) Secondary lymphedema: the middle section of lymphatic vessels, distal lymphatic vessels are dilated, tortuous, and increased in number and irregularity. Metastatic lymph nodes can be seen with filling defects and worm-like edges in the lymph nodes.
4.Complications
(1) Incisional infection, gonorrhea leakage.
(2) Systemic reactions: fever, nausea, vomiting, and peripheral circulation failure due to allergy to the contrast agent may occur individually.
(3) Local lymphatic vessels reactive inflammation, which aggravates lymphedema.
(4) Pulmonary embolism: The contrast agent may enter the vein through the anastomotic side branch and cause pulmonary embolism, with an incidence of 2-10%, and death due to pulmonary embolism has been reported in the literature.
(iii) Isotope lymphadenography Since lymphadenography does not provide quantitative kinetic information on the function of the lymphatic system, nor does it provide a simple picture of lymphatic drainage from different limb sites, a valuable static endolymphatic scintigraphy (nuclear imaging) is currently performed, in which 99mTc sulfide gel 0.25ml (75MBq) is injected into the subcutaneous tissue of the second toe web of both feet. Static image scans were made with an r camera facing the patient’s lower abdomen and inguinal region at 1/2, 1, 2 and 3 hours, respectively, and then the amount of isotope taken up by the iliac inguinal lymph nodes was calculated separately.
The study of lymphatic function in chronic lymphedema using isotope imaging suggested that the degree of reduced lymphatic return in the affected limb correlated with the severity of lymphedema. In severe lymphedema, the rate of isotope uptake was almost zero, whereas in venous lymphoedema the percentage uptake of lymphatic return was significantly increased. Therefore, it can be used to differentiate lymphoedema from venous edema with a sensitivity of 97% and specificity of 100% for the diagnosis of lymphoedema. Compared with lymphatic duct radiography, nuclear imaging is simple and diagnostic. However, it cannot localize the lymphatic vessels and lymph nodes anatomically. If lymphatic vessel surgery is considered, lymphatic vessel radiography is still preferred.
In addition, the newly developed technique of non-invasive vascular testing can also help to differentiate venous edema from lymphoedema, which is a simple and convenient screening test as an outpatient.
Differential diagnosis
In the early stage, due to the mild skin and subcutaneous tissue changes, it should be distinguished from other diseases as follows.
1. Venous edema is mostly seen in deep vein thrombosis of lower limbs, with acute onset of sudden unilateral limb swelling, accompanied by skin bruising, obvious pressure pain in gastrocnemius and femoral triangle, and exposure of superficial veins as its clinical characteristics, and dorsal foot edema is not obvious. Lymphedema starts more slowly, and swelling of the dorsal foot and ankle is more common.
2. Angioneurotic edema occurs due to the stimulation of external allergic factors, with rapid onset and fading, and is characterized by intermittent onset. Lymphedema has a tendency to increase gradually.
3. Systemic diseases Hypoproteinemia, heart failure, kidney disease, liver cirrhosis, mucinous edema, etc. can all produce lower limb edema. It is usually bilateral and symmetrical with clinical manifestations of the respective primary diseases. It is usually identified by detailed history, careful physical examination and necessary laboratory tests.
4, congenital arteriovenous fistula Congenital arteriovenous fistula can be manifested as limb edema, but generally the affected limb is larger in length and circumference than the healthy side, with increased skin temperature, superficial varicose veins, vascular murmurs can be heard in the local area, and the oxygen content of peripheral venous blood is close to that of arterial blood. All of the above are unique features.
5.Lipoma A few lipomas or adipose tissue hyperplasia with very extensive lesions can be confused with lymphedema. However, most of the lipomas are limited in growth, slow in course, soft subcutaneous tissues without edema, and soft tissue X-ray mammography is feasible to help confirm the diagnosis if necessary.
Prevention of lymphedema For secondary lymphedema, there are two groups of people who are susceptible: patients who have undergone radical surgery and radiation therapy for malignant tumors (e.g., breast cancer, ovarian cancer, uterine cancer, prostate cancer, intestinal cancer, bladder cancer, melanoma); and patients who have frequent episodes of cutaneous “dermatitis”.
The first group of patients should avoid damage to the skin of the affected limb after surgery and should not be injected on the affected limb and pay attention to the cleanliness of the skin. In addition, patients who have had filarial infections are also susceptible. Once edema is detected, immediate medical attention should be sought.
Patients in the second category should actively treat the initiating factors that led to the infection such as tinea pedis and strengthen the body’s resistance. If you find redness and fever in the skin or discomfort in the body similar to a cold, you should immediately use antibacterial agents to control the development of inflammation in a timely manner. If swelling of the back of the foot is found, it should be taken seriously and medical attention should be sought early.
VII. Treatment measures
Lymphedema has different treatment principles according to the early and late stages of the disease. In the early stage, the aim is to remove the depressed and stagnant lymphatic fluid and prevent the regeneration of lymphatic fluid, while in the late stage, the aim is to surgically remove the irrecoverable diseased tissue or treat the limited lymphatic obstruction by shunt.
(a) In the acute stage of lymphedema, non-surgical treatment is the main purpose.
1, postural drainage The lower limb sagging state makes the lymphatic fluid retention in the tissue space aggravated, elevating the affected limb 30-40cm using the effect of gravity can promote lymphatic fluid reflux and reduce edema. This is simple and effective, but the effect is not long-lasting, and the edema of the affected limb is aggravated again.
2.Pressure bandage On the basis of postural drainage, compression bandage is applied to the affected limb with elastic stocking or elastic bandage to squeeze the tissue gap and assist lymphatic reflux. The elastic bandage should be suitable for elasticity. Intermittent compression pumps can also be used for several times and for a long time to improve edema with certain effect. The literature reports that foreign countries are currently using lymphatic compression device (lymha-press) a more advanced and effective pressure inflating device, inflating device is divided into 9 to 12 blocks, each block can be individually inflated and pressurized, pressure from the distal end of the limb gradually to the proximal end, a cycle of 25 less.
This kind of lymphatic compression Shun than other simple compression device inflation pressure time is greatly shortened (simple compression inflation device cycle cycle of about 100 seconds), while can produce higher pressure up to 15.6 ~ 20.8kPa (120 ~ 160mmHg), more effective than surgical and simple elastic stockings in reducing swelling. However, it is more complicated to use and cannot reduce the protein component in the tissue interstitium, so it is only suitable for short-term treatment such as acute phase and preoperative preparation.
3. Restrict sodium intake and use diuretics Appropriate restriction of sodium chloride intake in the acute phase, generally 1 to 2g/d, to reduce tissue sodium and water retention. At the same time, use appropriate amount of diuretics to accelerate water and sodium excretion. Use dihydrocoumaric acid 25mg each time, 3 times a day, and appropriate potassium supplementation, and stop taking it after the condition is stabilized.
4, the prevention of infection selected antifungal ointment, powder, keep the toe dry is the most effective way to prevent and control fungal infections; toe nail bed under the bacterial infection is also more common, should be diligent to cut fingernails, remove dirt, reduce the path of bacterial invasion. When the streptococcal infection systemic symptoms, should be selected with penicillin and other drugs, with bed rest, and actively control the infection. Late stage lymphedema complicated by skin chapping can be protected and lubricated by applying ointment externally.
In addition, a variety of vaccines, milk and heterosexual protein injections are long-used anti-infection therapies. Various defense mechanisms of the human body are improved by this. Foreign scholars have proved that the lymphocytes in the output lymphatic vessels are increased and the gammaglobulin in the blood is raised during the injection of typhoid triple vaccine, which has the effect of preventing the occurrence of permanent lymphatic obstruction. Some authors speculate that the heterogeneous protein may act through the pituitary and adrenal glands.
(B) chronic lymphedema, including non-surgical treatment of baking bandage therapy and various surgical treatment.
1, baking bandage therapy Baking bandage therapy is a treatment method to explore the heritage of Chinese medicine. Its treatment principle is the use of continuous radiation heat, so that the affected limb skin vasodilatation, a lot of sweating, the local tissue interstitial fluid back into the blood, improve lymphatic circulation. For lymphedema has not yet occurred in the limb skin serious hyperplasia can be selected baking bandage therapy. There are two methods of electric radiation heat therapy and oven heating.
The temperature is controlled at 80~100℃, once a day for 1 hour, 20 times as a course of treatment. Each course of treatment interval 1 to 2 weeks. After each treatment, an additional elastic bandage should be applied. According to clinical observation, after 1 to 2 courses of treatment, it can be seen that the tissue of the affected limb is softened and the limb is gradually reduced, especially the number of episodes of dermatitis-like attacks is greatly reduced or stopped.
2.Surgical treatment Most lymphedema does not require surgery. About 15% of primary lymphedema eventually need to perform lower limb plastic surgery. Existing surgical methods except amputation can not cure lymphedema, but can significantly improve the symptoms.
(1) Indications for surgery.
(1) Impairment of limb function: easy fatigue and joint movement limitation due to heavy limbs.
(2) Excessive swelling with pain.
③Recurrent cellulitis and lymphangitis that have been ineffective by medical treatment.
④Lymphangioleiomyosarcoma: a lethal cause of long-term lymphedema malignancy.
⑤Cosmetic: Most patients with primary lymphedema are young women, and surgery can be considered for those with obvious swelling and cosmetic requirements, but the main focus should be on improving function, and cosmetic countries should be supplemented, otherwise the efficacy may not be satisfactory.
Pre-operative preparation and post-operative treatment.
(2) Pre-operative preparations play an important role in the outcome of surgery. They include.
① Bed rest to elevate the affected limb: to reduce limb edema to a minimum. There are methods such as lower limb padding, lower limb suspension and bone traction, and lower limb elevation of 60º is appropriate.
②Control of infection: for recurrent acute cellulitis and acute lymphangitis, sensitive drugs should be selected to be administered intravenously or intramuscularly before and during surgery to reduce the chance of postoperative flap infection.
③Cleaning the skin: to achieve ulcer healing or control local infection.
④Keep the postoperative drainage open; the separated rough surface may have continuous capillary blood leakage. Negative pressure drainage must be placed to keep no accumulation of blood and fluid under the flap, to reduce the factors affecting the blood supply of the flap, to prevent flap blanching and infection, and to reduce the rate of surgical failure.
⑤ Continue to elevate the affected limb after surgery to reduce edema in the affected limb and facilitate venous and lymphatic reflux.
(3) Surgical classification: Lymphedema surgery can be divided into two categories.
① Extensive excision of diseased tissue.
②Lymphatic reflux reconstruction.
According to experimental and clinical evidence, some or most of the good results of the latter are in fact achieved on the basis of extensive lesion tissue excision. Reconstruction of lymphatic reflux alone is a very delicate surgical operation, but has little efficacy. Since the lymphatic system is intact proximal and distal to the point of lymphatic vessel obstruction in secondary lymphedema, surgical reconstruction of regional lymphatic return should yield good results. Conversely, most primary lymphedema has poorly developed proximal and distal lymphatic vessels and cannot be improved by the expectation that reconstructive lymphatic return surgery will improve symptoms.