Managing Lymphedema: Treatment Options for Quality of Life

Historically, lymphedema has been underestimated in clinical practice and education, to the detriment of many patients with this pathology. The advent of new surgical options, as well as tools that allow for earlier diagnosis, has improved the lives of patients.

However, lymphedema remains an incurable disease. Many physicians encounter difficulties lacking formal training in assessment and management.

The objective of this article is to offer guidance in diagnostic evaluations and prioritize therapeutic options, as well as highlight the fundamental characteristics of the condition.

Lymphedema is classified as primary or secondary . Primary lymphedema occurs in individuals with innate dysfunction, commonly agenesis or hypogenesis of their lymphatic vessels.

Primary or hereditary lymphedema is characteristically subdivided into categories according to the age of onset of symptoms: Nonne-Milroyd disease-congenital hereditary lymphedema (at birth or within the first 2 years of life), Meiged disease-familial early lymphedema ( during puberty) and late-onset lymphedema, which generally occurs after age 35.

Secondary lymphedema is more prevalent and develops when intact lymphatics become obstructed or suffer iatrogenic, infectious, inflammatory, surgical, or traumatic damage. Filarial infection in countries with developing economies remains the most common cause of secondary lymphedema. In countries with developed economies, lymphatic resection and irradiation for staging or monitoring of locoregional cancer is the most common cause. However, the obesity pandemic has produced a rapidly growing subgroup of patients.

People at risk for lymphedema are defined as those who have not yet shown signs and symptoms consistent with a diagnosis of lymphedema but who have known insufficiency of their lymphatic system. This group includes, but is not limited to, anyone who has had lymph nodes removed or received radiation therapy during cancer treatment. Additionally, people who have family members with hereditary lymphedema may also be at risk.

Regular follow-up visits are recommended and should include extremity measurements, assessment of post-treatment physical decline, functional status, and subjective self-report of symptoms. Body weight should be maintained within normal standards. Aerobic and weight-bearing (anaerobic) exercise adapted to individual needs is suggested.

Regarding breast cancer patients , several actions may not significantly reduce their risk of breast cancer-related lymphedema (BCRL).

The lymphatic anatomy adapts to the requirements of its main functions. The first of them, the sequestration of solid macromolecular interstitial debris, is directly related to the second, immunological surveillance. The more distal elements of the lymphatic system barely distinguish between microbes and molecules, both being transported to the lymph nodes for processing.

Unlike veins, the walls of the collecting vessels, which transport lymph proximally, are lined with smooth muscle that allows the propulsion of lymph peristaltically. Sympathetic stimuli activate myocytes in lymph collecting vessels, allowing the system to dramatically increase lymph flow under conditions of increased production, such as occurs with exercise.

The lymphatic collectors end in the lymph nodes, where waste filtration, identification of potentially harmful pathogens, and regulation of lymph viscosity occur. Finally, it returns to the systemic venous circulation.

When the lymphatic load exceeds the transport capacity of the lymphatic system, dynamic insufficiency occurs.

In this scenario, the lymphatic vessels are intact but overloaded. This situation results in the accumulation of tissue fluid that is successfully treated with elevation or compression of the extremity. In contrast, mechanical or low-volume insufficiency of the lymphatic system produces lymphedema.

Mechanical insufficiency can be caused by hypogenesis or agenesis of the lymphatic vessels, alteration of the activity of the lymphatic pump, increased lymphatic permeability that favors the entry of proteins from the lumen into the interstitial fluid, inflammatory response, lymphatic obstruction or surgical removal. of the lymph nodes.

In the absence of treatment, lymphedema progresses over time and more rapidly in the lower extremities. Lymphedematous progression is divided into 4 sequential stages ( table ).

Chronic inflammation is hypothesized to initiate the progression of lymphedema. Macromolecular debris stimulates the migration of neutrophils and macrophages, triggering fibroblast recruitment. These activated cells make collagen, which becomes an extensive disorganized matrix of scar tissue that further traps lymphatic vessels, impeding their physiological activities.

Distinctions between stages I and II are usually based on palpation, and a diagnosis of stage I is made if easy pitting is seen and there are no foci of taut, rubbery tissue. Thickening over the dorsal fingers and interphalangeal joints is practically pathognomonic of lymphedema. Stage III lymphedema is distinguished only by the presence of skin changes: keratinization and papillomas.

The differential diagnosis of chronic swelling in the absence of lymphatic involvement includes lipedema, lymphedema syndromes (Klippel-Trenaunay, Noonan, and Turner syndromes), anasarca, organ failure, and venous insufficiency. Venous insufficiency is the most prevalent and difficult to distinguish because it can occur locally in the absence of other signs or symptoms and often coexists with lymphatic involvement.

Involvement of the dorsum of the foot, soft tissue thickening, Stemmer’s sign, and characteristic skin changes suggest lymphatic involvement. In contrast, the presence of inverted champagne bottle lipodermatosclerosis and hemosiderin staining of the skin imply venous stasis.

Identification of the primary contributor can inform prognosis, treatment components, risk of specific complications, and follow-up plan.

It is essential to have baseline measurements of the ipsilateral and contralateral extremities, which is vital to establish the relationship between the two and monitor weight gain or loss. Similarly, follow-up strategies should be developed to detect lymphedema. The ideal diagnostic test is a non-invasive, cost-effective and reliable examination with minimal inter- and intra-rater variability.

> Non-invasive measurements

Limb volume (VE) or circumference measurements are used to clinically evaluate lymphedema. The most common way to clinically evaluate the function and structure of the lymphatic system is simply by using a tape measure. This process is a reliable method for detection and control.

The doctor can measure VE with water displacement, perometry, or multifrequency bioimpedance measurements. These automated VE scanning methods eliminate interobserver variability but are more expensive.

​>  Image measurements

Imaging techniques in lymphedema are essential for diagnosis, treatment planning and determination of subsequent progression.

Lymphoscintigraphy involves intradermal injection of radiolabeled colloid and subsequent imaging of the lymphatic system. This technique allows visualization of both lymphatic function and anatomy. Additionally, quantitative analysis may reveal increased cleanup time from the injection site and the level of detectable radioactive waste.

The application of magnetic resonance angiography and magnetic resonance lymphangiography to the diagnosis of lymphedema allowed a higher level of resolution with fewer artifacts and without ionizing radiation.

Another valuable modality is computed tomography, which also allows simultaneous diagnosis of deep vein thrombosis, hematomas, cellulitis, and cysts. However, patients are exposed to radiation, and a relatively lower level of diagnostic and prognostic accuracy makes it not an ideal first-line option.

The current international standard for the initial treatment of lymphedema remains manual and is called complete or complex decongestive therapy , which includes an intensive, step-down phase 1 and a maintenance phase 2.

Phase 1 includes manual lymphatic drainage, a massage technique developed to stimulate smooth muscle contractions in the lymphatic collecting vessels; short stretch compression bandage; repetitive limb movements to create an internal pumping action; skin care; and self-management instruction.

Compression garments worn during waking hours are the mainstay of phase 2 lymphedema maintenance therapy . Garments vary widely in compression, degree of coverage, fabric, and cost.

Surgical intervention is offered to patients in whom conservative treatment has failed.

Nonsurgical management remains the first-line approach and criterion standard, although it is labor-intensive and requires strict compliance and lifelong commitment.

Patients in the earliest stages (I and II) are offered surgical treatment if they have been symptomatic for more than 12 months and have undergone at least 6 months of complex decongestive therapy without improvement. In the most severe stages (stage III), patients can be offered surgical treatment without failing conservative treatment if they have been symptomatic for more than 12 months.

Surgical management of lymphedema can be broadly divided into 2 categories: physiological and excisional. Physiological procedures use microsurgical techniques to restore lymph flow. Alternatively, reduction procedures remove lymphedematous fibrotic tissue. Currently, there are no established guidelines for the type of procedure, patient selection, and timing of the intervention.

In general, it is believed that physiological approaches lead to better results in the early stages because there is some remaining lymph flow and less fibrotic tissue. Reductive approaches are considered best for addressing very advanced stages where volume reduction can only be achieved by tissue excision.

> Lymphatic bypass

It involves harvesting healthy lymphatic vessels as a composite graft; They are completely removed from the body and implanted in the affected region. The harvested lymphatic is buried in the subcutaneous tissue and microscopically anastomosed to the recipient’s lymphatics.

Another surgical approach has been to bypass the lymphatic vessels and drain directly into the venous system. It is called lymphovenous bypass (LVB) or lymphaticvenular anastomosis (LVA), depending on the caliber of veins used.

> Transfer of vascularized lymph nodes

The transfer of lymph nodes from unaffected regions as vascularized free tissue transfer and their placement in the affected extremity using microsurgical techniques is called vascularized lymph node transfer (VLNT).

This approach reconstitutes lymph flow in areas of previous lymph node dissection or allows neolymphatic regeneration in nonanatomic areas such as the wrist or ankle distally or the groin or axilla proximally.

> Transfer of vascularized lymphatic vessels

Despite the high success of VLNT and LVA, both surgical options are not without limitations. An LVA is contraindicated in advanced stages in which the lymphatic vessels are severely damaged and sclerotic, while VLNT carries the no less serious risk of iatrogenic donor site lymphedema.

A technique with vessel transfer based on the first dorsal metatarsal artery was developed. The main advantages of these methods are less invasiveness with small incisions, faster flap elevation, and low complication rate.

> Preventive procedures in primary surgical intervention in patients with breast cancer

With increasing evidence of favorable outcomes with physiologic approaches, some investigators have shifted focus to risk reduction with lymphedema prophylactic procedures in breast cancer patients in an attempt to prevent BCRL. It involves injecting blue dye into the arm to visualize lymphatic drainage in the arm. During sentinel lymph node biopsy, an attempt is made to protect these lymphatic vessels, thus preserving lymph flow draining from the arm.

A radical excision of the limb with preservation of skin perforators, a technique known as radical reduction with preservation of skin perforators, is possible. This approach provides effective reduction of lymphedematous tissue and restoration of limb function while minimizing the risk of poor cosmesis. The procedure is usually performed for lymphedema of the upper extremities

For cases of severe and refractory lymphedema, a more aggressive approach is taken with the Charles procedure, which involves complete removal of the skin and subcutaneous tissue and placement of skin grafts from the resected specimen to the underlying deep fascia. Typically, these procedures are used for the lower extremity due to poor aesthetics.

Removal of irreversibly damaged tissue appears to be essential in a holistic therapeutic approach. This step is particularly relevant for end-stage extremity lymphedema in which chronic inflammation ultimately leads to increased collagen deposition and extracellular matrix remodeling.

Early detection and education are key to controlling lymphedema. Lifestyle restrictions based on myths or widespread misperceptions have a negative impact on patients’ ability to continue living and enjoy life.

Complex decongestive therapy remains the mainstay of treatment. Once lymphedema develops, surgical options are now available and can be offered to patients who have failed conservative treatment.

A personalized approach with careful patient selection is the cornerstone of current surgical treatment of patients with lymphedema. Aside from these general considerations, there is substantial variety in the surgical techniques used by surgeons.

A better understanding of the nature of the disease and the different treatment options will allow the healthcare team to provide more comprehensive care to patients with lymphedema.