Lower Extremity Lymphedema; An Often Overlooked and Undermanaged Condition

The components of CDPT are implemented and facilitated by a trained lymphedema specialist during the intensive phase and include:

1. Meticulous skin and nail care to the affected areas

2. Manual lymphatic drainage (MLD), which is a gentle manual technique that redirects lymph flow

3. Multilayer, short-strech compression bandaging during active decongestion, and over-the-counter or custom garments once the limb has decongested

4. Therapeutic exercise to enchance and promote lympathic pumping mirrors the effects of MLD, with patient reports of ease of use and comfort, without an increase in pain scores75

Additionally, during the maintenance phase, the utilization of intermittent pneumatic compression (IPC) may be employed as an adjunctive device to help maintain fluid reduction.

Of note is the growing understanding of the effects of manual lymph drainage beyond the reduction of fluid volume. Emerging evidence is highlighting the impact MLD has on soft tissue remodeling, and the resolution and prevention of soft tissue dysfunction. To appreciate this, it is important to understand the inter-relationship between the lymphatic and integumentary systems.

9a: Negative Bjork ‘bow tie’ test.

9b: Positive Bjork ‘bow tie’ test.

9c: ‘Bow tie’ of wrinkles in negative test.65

When lymphatic fluid is stagnant, a pathohistological state of chronic inflammation results.76 This chronic inflammatory state induces a cascade of events that results in connective tissue proliferation and excess collagen tissue formation, culminating in the thickened, fibrotic skin and wart-like projections (papillomatosis and verrucous) commonly seen with chronic lymphedema.77 Further, disorders of the lymph system, whether systemic (macro-lymphedema) or localized (micro-lymphedema), produce cutaneous regions susceptible to infection, inflammation and carcinogenesis.77 The chronic inflammation resulting from lymphedema creates a region of cutaneous immune deficiency, or a localized skin barrier failure; the associated abnormalities are called lymphostatic dermopathy, which is the failure of the skin as an immune organ.61,77,78 Areas of lymphostatic dermopathy are often associated with the presence of chronic wounds and chronic infections.

Manual lymph drainage helps to re-route stagnant lymph fluid to functional lymphatics, thereby mobilizing the fluid and reducing limb volume. This is coupled with the fact that mobilizing the stagnant lymph breaks the chronic inflammatory cycle and the deleterious integumentary sequelae that ensues. A growing body of evidence is shedding light on the positive effects MLD has on many structures and conditions. Although beyond the scope of this article, the following highlights the current evidence in support of MLD: the evidence supports MLD for influencing soft tissue remodeling;79,80 synergistic effects when combined with exercise;81 positive effects on the veins and venous ulceration;82,83,84,85,86 improving orthopedic outcomes such as total knee replacements;87,88,89 and MLD is beneficial for other diagnoses such as orthopedic injuries,90 neurological diseases, autoimmune diseases, autism, when combined with Proprioception Neuromuscular Facilitation.91,92,93,94,95 The benefits of MLD have been assessed using near-infrared fluorescence imaging evaluating pre- and post-therapy sessions, and illustrating improved contractile lymphatic function.96

It is well understood that lymphedema can be a complex and challenging condition to manage. This is further evidenced by a report that lymphedema patients seen in an outpatient wound clinic had an average of 7.3 comorbidities and took 8.4 concomitant medications.7 To assist healthcare providers in managing these complex patients, the Lower Extremity Lymphedema Complexity Score (LLCS) has been created.97

The tool is meant to help clinicians identify the various contributing factors and complexities of patients presenting with lymphedema and skin impairments. This could help drive proper examination and differential diagnosis, treatment planning, as well as utilization of proper resources. The LLCS contains 12 domains: comorbidities (referring to any copresenting condition that impacts overall health), limb edema, tissue texture, scars, skin integrity, skin changes, fat disorders (lipedema), BMI, mobility, activities of daily living (ADLs), pain/ discomfort and the Lymphedema Life Impact Scale (LLIS, used with permission from the author).

The 12 established domains reflect common presentations ranging in complexity that can contribute to lymphedema severity and complications. Each domain is to be scored based upon the complexity of the condition, ranging from nominal complexity (0), mild complexity (1), moderate complexity (2), severe complexity (3) or extreme complexity (4). If a patient has bilateral lymphedema, the score is based on the most complex or involved limb. Descriptions under each domain and section are provided for additional clarity. A cumulative score will indicate if the patient presents with mild, moderate, severe or extreme complexity.

The next phase in the development of the LLCS is to create algorithms of suggested interventions and/ or referrals based upon standards of practice and evidence-based medicine. Though not prescriptive, the algorithms are meant to provide guidance and suggestions for healthcare providers as to how best manage the common associated complications and underlying pathologies widespread in this patient population.

Intermittent pneumatic compression pumps (IPCs) are available as simple (leg sleeves) and advanced (leg sleeves with an abdominal component). In addition, available IPCs have varying mechanisms of action, including push and squeeze, push-squeeze-pull, and pull. Push and squeeze IPC devices are typically high pressure and show a dose-dependent relationship between pressure and total fluid flow rates.98 At times, this can be beneficial as patients with later stage lymphedema often have epidermal and dermal thickening and fibrotic changes often requiring more force to move fluid.99 Consequently, high flow and pressure rates can also lead to collateral channel formation lacking lymphatic endothelial lining, therefore lacking the clinical benefits of the glycocalyx. Push-squeeze-pull IPC devices often cycle between pressures while completely deflating between compression phases. Pull IPC devices most closely mimic the suction theory and MLD by facilitating the subatmospheric environment of tissue beds and allowing interstitial fluid to be drawn into the lymphatic vasculature. The goal with IPC devices and conventional therapy on fluid redistribution is to promote lymphangiogenesisvia stimulation of local mediators and promote native lymphatic function.100,101,102

The push-squeeze-pull mechanism commonly seen in advanced IPC devices have been evaluated with Near InfraRed Florescence Imaging (NIRFLI) to effectively move lymphatic fluid proximally, similar in manner in which NIRFLI demonstrated the effectiveness of MLD.103,104,105

The purpose of the abdominal component in advanced IPC devices is to ‘prime’ the receiving abdominal and upper thigh lymphatics, creating receptive capacitance as the pump ‘cycles’ through the abdominal chambers, initially to clear the underlying lymphatic vasculature with subsequent initiation of the leg sleeve chambers propagating distally from the ankles to the thighs. The advanced pumps mimic the cycling treatments of MLD therapy, maximizing extremity treatment.

For patients deemed to be appropriate candidates for an IPC, outcomes are best when used in conjunction with a physical medicine and rehabilitation/ vascular/ lymphatic specialist, and/ or a certified lymphedema therapist (CLT), providing treatments and education; MLD, CDPT, stretching, exercise, nutrition, and skin care remain critical elements of daily treatment. Also, because patients with lymphedema may present in various clinical settings, it is prudent for education awareness on the appropriate referral and management options that exist.

Multiple benefits of IPC devices are recognized, including patient access to use on a daily basis, utilization in locations where access to healthcare may be limited, and peer reviewed data demonstrating improved medical outcomes associated with decreasing overall medical resource utilization.106,107,108 In addition, advanced pneumatic compression devices have been shown to have significant economic and quality of life benefits when compared to conservative treatment. Advanced IPC use has been shown to reduce phlebolymphedema and phlebolymphedema sequelae related costs annually by 69%, including 59% reduction in hospitalizations, 82% lower inpatient costs, 55% lower outpatient costs, and reduction in physical and occupational therapy costs.108 In addition to the economic benefit, utilization of IPC can also lead to improved quality of life for patients.

Surgical Management of Lymphedema

Pharmacotherapy

Multiple over the counter medications tout a venotonic or lymphotonic effect; regarding many components present in over the counter medications, quality peer reviewed publications are limited. Flavonoids are a phenolic plant derived compound found in over 8000 different forms, with multiple biological properties109 and are among the most studied medications for management of lymphedema associated with chronic venous insufficiency. The specific flavonoids, hesperidin and diosmin, were evaluated in a 2017 meta-analysis, identifying moderate quality evidence demonstrating benefit for management of venous ulcerations and edema (phlebolymphedema).110 Diosmin, as a component of a hybrid medication, was found to improve outcomes when used in conjunction with CDT as compared to CDT alone.111 Diosmin formulations are commercially available in the U.S., including Vasculera’s diosmiplex, a proprietary micronized blend of purified diosmin glycoside and alkyline granules. Use of the FDA regulated Diosmiplex has been shown to have therapeutic value, although initially mislabeled in a recent publication in Wounds 2020 that has been since corrected.112

Micronized purified flavonoid fraction (MPFF) has been shown to decrease the inflammatory cascade and leukocyte-endothelial activation, thereby discouraging edema formation.113 MPFF consists of 90% diosmin and 10% hesperidin and supplementary flavonoids, and comes from extracts of rutaceaeaurantiae, a type of small orange that is micronized for improved bioavailability.113,114 MPFF has not been associated with known major side effects, while simultaneously showing significant improvement in quality of life in patients with chronic venous insufficiency, and accelerated healing of leg ulcers.113,115,116,117 Similarly, selenium has been noted to have a positive impact on lymphedema symptoms in a recent literature review.118 Often considered for patients with lymphedema undergoing long-distance travel or flight is the use of pinus pinaster bark extract (PBE), which goes by the tradename Pycnogenol. PBE possesses vasorelaxant activity, and enhances microcirculation through increasing capillary permeability. PBE has been shown to be effective in improving leg heaviness, subcutaneous edema, and venous pressure in patients with chronic venous insufficiency.119

Patients should also be educated in skin care, including use of a ceramide based hydrating cream to maintain dermal integrity and hydration, in order to decrease micro-cracks that leave the patient susceptible to episodes of cellulitis and erysipelas. As lymphatic dysfunction progresses, the immune function of the lymphatics is also impaired, thereby increasing patient risk of infection. Immediate access to antibiotics via an up to date prescription is generally recommended to minimize the intensity and duration of an episode of cellulitis. For patients with recurrent cellulitic episodes, chronic prophylaxis may be the best management option to prevent persistent demise of already compromised lymphatics. It is well established that with every additional cellulitic episode there is further damage to the lymphatic system, causing a degree of secondary lymphedema.120,121 This creates a cyclical problem, as the already compromised lymphatics are susceptible to infection, which in return potentiates further lymphatic damage.122 It should be noted that there is no current recommended diet for the management of lymphedema; some patients are instructed to limit water or protein intake, however this is not supported by the literature.123,124

Conclusion

Current medical and clinical education regarding the anatomical and pathophysiological state of lymphedema have far lagged behind the rapidly advancing field of lymphatic medicine. Consequently, the accurate and evidencedbased approach to lymphedema assessment and management are not unanimously and universally employed. This paper seeks to outline the basic fundamental structure of the lymphatic vasculature and its importance in lymphatic function. As patients with lymphedema often present in a myriad of different clinical settings, it is important to deploy accurate clinical assessment and readily offer best practice management options. These management options should include meticulous skin and nail care, manual lymphatic drainage, compression, therapeutic exercise, and review of pharmacologic options. As chronic lymphedema will likely require chronic management, the use and application of IPC devices is also discussed. The use of IPC devices as adjuncts to traditional therapy can be used to decrease lymphedema related complications and improve patient quality of life. In addition, IPC devices have the ability to be used in regions where limited lymphedema therapists or specialists exist, thereby continuing to provide patients with lymphatic stimulation. The goal of MLD or IPC devices is to stimulate the underlying lymphatic system, to redistribute stagnant lymph as outlined by the revised starling curve; by redistributing stagnant lymph back into circulation the not uncommon lymphedema sequelae of recurrent infection, ulceration, deformity, and dermal/ epidermal skin changes can be minimized.

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