As the disorder progresses, worsening edema and skin changes including discoloration, verrucous (wart-like) hyperplasia, hyperkeratosis, papillomatosis, dermal thickening, and ulcers may be seen.

Left untreated, this stagnant, protein-rich fluid causes tissue channels to increase in size and number, reducing oxygen availability.

[citation needed] In rare cases, lymphedema may lead to a form of cancer called lymphangiosarcoma, although the mechanism of carcinogenesis is not understood.

[medical citation needed] Lymphedema may also be associated with accidents or certain diseases or conditions that may inhibit the lymphatic system from functioning properly.

[12] In tropical areas of the world where parasitic filarial worms are endemic, a common cause of secondary lymphedema is filariasis.

[4][citation needed] Secondary lymphedema affects both men and women, and, in Western countries, is most commonly due to cancer treatment.

It may also occur in the lower limbs or groin after surgery for colon, ovarian or uterine cancer, if removal of lymph nodes or radiation therapy is required.

Surgery or treatment for prostate, colon and testicular cancers may result in secondary lymphedema, particularly when lymph nodes have been removed or damaged.

[medical citation needed] The onset of secondary lymphedema in patients who have had cancer surgery has also been linked to aircraft flight (likely due to decreased cabin pressure or relative immobility).

For cancer survivors wearing a prescribed and properly fitted compression garment may help decrease swelling during air travel.

[22] Some cases of lower-limb lymphedema have been associated with the use of tamoxifen, due to blood clots and deep vein thrombosis (DVT) associated with this medication.

This deficiency is a grouping of several disorders caused by a single defect: familial or sporadic inactivating mutations in one of the two parental GATA2 genes.

The GATA2 protein is a transcription factor critical for the development, maintenance, and functionality of blood-forming, lymphatic-forming, and other tissue-forming stem cells.

GATA2 deficiency-induced defects in the lymphatic vessels and valves underlies the development of lymphedema, primarily in the lower extremities but may also occur in places such as the face or testes.

This form of the deficiency, when coupled with sensorineural hearing loss, which may also be due to faulty development of the lymphatic system, is sometimes termed Emberger syndrome.

Treatment with QBX258 has been found to decrease hyperkeratosis and fibrosis, reduce the number of CD4+ cells, and normalize the expression of Th2-inducing cytokines and IL13R by keratinocytes.

[31] Studies have revealed that sustained lymphatic stasis results in the infiltration of CD4+ T-cells, leading to inflammation and fibrosis within affected tissues.

Assessment of the extremities first begins with a visual inspection; color, presence of hair, visible veins, size and any sores or ulcerations are noted.

Enlargement of the nodes lasting more than three weeks may indicate infection or other illnesses (such as sequela from breast cancer surgery) requiring further medical attention.

[35] Devices like SOZO [36] utilize Bioimpedence Analysis (BIA) by sending a current through the body and measuring the resultant impedance.

[citation needed] The International Society of Lymphology (ISL) Staging System is based solely on subjective symptoms, making it prone to substantial observer bias.

[39][40][41] As described by the Fifth WHO Expert Committee on Filariasis,[43][44] and endorsed by the American Society of Lymphology,[45][citation needed] the staging system helps to identify the severity of lymphedema.

With the assistance of medical imaging, such as MRI or CT, staging can be established by the physician, and therapeutic or medical interventions may be applied:[citation needed] Lymphedema can also be categorized by its severity (usually compared to a healthy extremity):[46] Lymphedema should not be confused with edema arising from chronic venous insufficiency, which is caused by compromise of venous drainage rather than lymphatic drainage.

[50] In breast cancer-related lymphedema, MLD is safe and may offer added benefit to compression bandages for reducing swelling.

Elastic compression garments are worn on the affected limb following complete de-congestive therapy to maintain edema reduction.

In some cases, pump therapy helps soften fibrotic tissue and therefore potentially enable more efficient lymphatic drainage.

[57][58] Moreover, resistance training and other forms of exercise were not associated with an increased risk of developing lymphedema in people who previously received breast cancer-related treatment.

[62] Vascularized lymph node transfers (VLNT) and lymphovenous bypass are supported by tentative evidence as of 2017[update] but are associated with a number of complications.

[2][example needed] Low-level laser therapy (LLLT) was cleared by the US Food and Drug Administration (FDA) for the treatment of lymphedema in November 2006.

Two cycles of laser treatment were found to reduce the volume of the affected arm in approximately one-third of people with post-mastectomy lymphedema at three months post-treatment.