Lymphedema

Primary or secondary disorder of lymphatic drainage.

Hereditary Lymphedema.

Hereditary Lymphedema Type I (Nonne-Milroy Syndrome; Milroy Syndrome; Congenital Hereditary Lymphedema type): Present at birth with areas of swelling. The importance of the swelling tends to increase with age, especially during infancy.

Hereditary Lymphedema Type II (Meige Lymphedema; Familial Lymphedema Praecox; Hereditary Lymphedema Tarda): Usually develops during childhood, adolescence, or early adulthood. It produces severe swelling in areas below the waist. It usually includes red skin over areas of swelling and associated discomfort and/or inflammation.

Secondary Lymphedema: Results from inadequate lymphatic drainage as a result of various causes, such as surgery, recurrent lymphangitis, cellulitis, neoplastic invasion of lymphatics, fibrosis following radiotherapy, or scar formation.

Incidence for hereditary lymphedema is estimated at 1:10,000 individuals. However, the incidence for secondary lymphedema is significantly higher. Meige lymphedema represents 80% of all hereditary lymphedema.

Hereditary lymphedemas that are not associated with other malformations usually affect the lower limbs and are inherited as an autosomal dominant trait with variable penetrance (autosomal or sex-linked recessive forms are less common). These nonsyndromic hereditary lymphedemas are categorized by their age of onset, being either congenital (Milroy disease) or having an onset in childhood or around puberty (Meige disease). Lymphedema can been associated with various other anomalies, many of which are genetic (autosomal recessive, autosomal dominant or X-linked recessive inheritance), and with Turner and Noonan syndromes.

Several genes may be involved in the development of hereditary lymphedema, including the following:

• Vascular endothelial growth factor receptor 3 (VEGFR3), formerly known as FLT4, is located on chromosome 5.
• FOXC2, which is responsible for causing the lymphedema-distichiasis syndrome (16q24.3).
• At least one (more likely, several) other gene can be responsible for other forms of hereditary lymphedema.

In the primary forms, aplasia or hypoplasia of the lymphatic vessels results in dilatation of extralymphatic spaces. In both primary and secondary forms, lymphatic obstruction from any cause results in increased protein content of the extravascular tissue and, because of its osmotic effect, retention of additional water. This excess extravascular protein often leads to proliferation of fibroblasts and organization of the edema fluid, giving rise to a characteristic firm, nonpitting swelling.

Clinical findings, results of the patent blue test and fluorescence microlymphography, indirect lymphography, or isotope studies suffice for correct diagnosis. In hereditary lymphedema present at birth (Milroy disease), the lymphatic capillaries and precollectors are aplastic, whereas in sporadic lymphedema with postpubertal onset, the large collectors are hypoplastic or aplastic, and a well-developed superficial capillary network is detected.

The edema in Milroy disease is present from birth in contrast to the edema, particularly severe below the waist, that develops around puberty in Meige syndrome. Involvement of the upper limbs, face, and larynx are notable features in Meige syndrome. There is also an association with deafness, cleft palate, primary pulmonary hypertension, and cerebrovascular malformations. In the autosomal recessive form, there is intestinal lymphedema, facial anomalies (antimongoloid slant of palpebral fissures, euryblepharon, retrognathia, chemosis), coarctation of aorta, patent ductus arteriosus, and hypoalbuminemia. At the beginning, the edema is pitting and disappears with elevation of the affected part. Subsequently, with development of fibrosis, the edema becomes nonpitting. The overlying skin becomes hyperkeratotic and waters. Fissures and secondary infections often occur. Treatment is often symptomatic with elastic stocking, active muscle exercises, and centripetal massage. Diuretics may be used. Antibiotics are often required for recurrent infection. Surgical management of lymphedema does not amount to more than 10% of cases. Excisional procedures, such as the Thompson operation, are done. Liposuction is an attractive alternative. The most effective types of surgical treatment are microsurgical lymphovenous or lymphovenous-lymphatic bypass. Secondary lymphedema of the lower extremities (more rarely of the upper limbs) is the primary indication for surgical treatment.

Depending on the form of lymphedema, a detailed systematic review of the known involvement is necessary. In Milroy disease, particular attention should be paid to the presence of respiratory impairment potentially caused by pleural effusions and the hypoproteinemia secondary to chronic gastrointestinal protein loss. In Meige syndrome, the airway should be assessed with regard to the presence of cleft palate, laryngeal edema, and facial edema. Pulmonary hypertension should be excluded and any neurologic history or deficits noted. Investigations include complete cell blood count, coagulation status, serum protein and albumin levels, chest radiography, arterial blood gas analysis, serum electrolytes, ECG, echocardiography, and radionuclide imaging, if necessary, in the presence of pulmonary hypertension.

Monitoring and the anesthetic technique depend on the involvement of the various systems with regard to the type of lymphedema. In general, adequate venous access should be obtained if excision of the lymphatic system is to be performed. Adequate analgesia should be provided in such instances, as the amount of postoperative pain is significant. In all cases, proper positioning of the edematous parts is necessary to prevent trauma and sores. Stockings and pneumatic devices to reduce further dependency-related edema are useful for long operations. Thromboembolic prophylaxis should be considered.

Low serum protein levels result in a higher free drug concentration; consequently, the dose of drugs that are highly protein bound (e.g., thiopentone) needs to be carefully titrated. Potassium supplementation perioperatively may be required in those on long-term diuretic therapy.

Hereditary Angioedema: Vascular disorder characterized by edema on the back of the hands or feet, eyelids, lips, and genitals. Pruritus and urticaria are rarely present. It is inherited as an autosomal dominant trait.

Traumatic Lymphedema: Caused by injury to the lymph system. It is a localized lymphedema and is secondary to postinfectious syndromes, postradiation fibrosis, tumor growth, and surgery (e.g., mastectomy). Symptoms may include swelling, pitting, redness, discomfort, and/or tingling sensations.

Elephantiasis: An infectious tropical disease of the lymphatic system that is characterized by gross enlargement of an arm or leg or other areas of the trunk or head.