Clinical Evaluation of Lymphedema

Known Etiology of Lymphedema

The diagnosis of primary lymphedema was once applied to all lymphedemas that were not deemed as related to surgery or injury. Recent work has focused on the phenotyping of primary lymphedema and distinguishes between lymphedemas and lymphatic dysplasia and syndromes. Primary lymphedema can be clinically classified as “congenital lymphedema,” which can manifest as swelling from birth to 2 years of age; “lymphedema praecox,” from 2 to 35 years of age; or “lymphedema tarda,” onset after 35 years of age. Currently, focus is being placed on classifying nonsecondary lymphedemas into more condition-specific categories, clinically referred to as lymphatic dysplasias, or connecting the lymphatic disorder to a syndrome. In many cases, a malformation of the lymphatic system will be evident in imaging (e.g., aplasia, hyperplasia, or hypoplasia—see p. 4–5). Currently, at least 20 gene mutations have been identified that are associated with lymphedema. These include vascular endothelial growth factor receptor 3 ( VEGFR3 ), which is associated with some familial Milroy lymphedema, first described in 1998, and FOXC2 (for more details, see Brouillard et al.). Others still are yet to be identified, as there are classified lymphedema-associated syndromes without identified genetic mutations.

Secondary lymphedema is associated with an extrinsic event (e.g., cancer, radiation, vascular disorders, trauma, skin infections, operations). The most researched etiology for lymphedema is that secondary to breast cancer. This may be due to the large numbers in which lymphedema occurs and the years of survivorship possible with modern cancer treatment, as well as the high visibility of the swollen upper extremity. Lymphedema secondary to breast cancer can manifest itself in swelling of the whole upper quadrant of the truncal regions (front and back of the chest wall and arm); however, usually swelling (and sensation changes) will start in a specific region and in time will progress to other territories. Stanton et al. demonstrated in their study that the mechanism is not similar to a stopcock, rather the lymphatic change represents impaired function resulting in a regional swelling. Therefore, lymphedema can start at the forearm or the hand and proceed proximally or at the upper extremity proximally and proceed distally. There has been some work looking at genetic predisposition to developing secondary lymphedema, and this will continue to be an area of further research.

Another cause of secondary lymphedema is venous insufficiency in which the venous hypertension exceeds the lymphatic transport capacity leading to chronic edema complicated frequently by chronic ulcers. Chronic ulcers of various etiologies can occur when swelling is involved and can benefit from compression bandaging. However, proper wound care should be administered, and all the information regarding chronicity, depth, size, and treatment should be obtained in order for a good collaboration between healthcare providers and the lymphedema therapist.

Co-morbidities

Comorbidities involve other conditions that may cause swelling or exacerbate lymphedema ( Box 9.2 ) or that may be considered contraindications for lymphedema treatment ( Box 9.2 ). An example is chronic heart failure in which both legs may be edematous. This type of swelling should be treated with the appropriate cardiac care. However, if swelling persists after elevation and medication for the cardiac condition, compression bandaging can shift fluid centrally. A cardiologist should be consulted as treatment begins and continues.

Medications

Drugs that have a side effect of swelling ( Box 9.3 ) can either cause or exacerbate lymphedema. Swelling will not always appear immediately after taking the drugs; therefore, establishing causality is difficult. However, when there are other drugs available that do not cause swelling, these patients may benefit from these alternatives. When there is no possibility of replacing the drug and the edema is manageable (e.g., when swelling disappears with elevation), compression stockings can be provided for lymphedema care.

Social Situation and Level of Support

Armer published a model that showed that social support and coping style are protective mechanisms for outcomes of breast cancer–related lymphedema, such as quality of life and functional health status. In a clinical setting, a patient who has support from a family member may be able to adhere to the treatment regimen more readily than the patient who is coping alone.

Screening Tests

The purpose of screening tests, such as laboratory draws and ultrasound imaging or ankle-brachial pressure index (ABPI) testing ( Box 9.4 ), is to determine the etiology of edema, pain, or redness when clinical history and manifestation are not sufficient. Ruling out infection, vascular or arterial disease, lymphangiosis carcinomatosa, and other morbidities or conditions must occur before a diagnosis of lymphedema can be made and corresponding therapies initiated. When diagnosis of lymphedema is uncertain or difficult, referral to a lymphologist or physiatrist experienced in lymphedema is recommended. For example, redness of the skin that accompanies swelling can be caused by erysipelas infection. However, lymphangiosis carcinomatosa (an inflammation of the lymph vessels which can be associated with cancer) can manifest in the same way. Laboratory assessment for infection may demonstrate a pronounced leukocytosis, elevated C-reactive protein (CRP), and the blood cultures which are positive for group A streptococci (indicating erysipelas) or Staphylococcus aureus .