Approach Considerations
The goal of lymphedema therapy is to restore function, reduce physical and psychologic suffering, and prevent the development of infection.
Initiate therapy for lymphedema as early as possible before extensive, irreversible fibrosclerotic changes occur in the interstitium. Strict compliance with treatment techniques is essential, even though they are often cumbersome, uncomfortable, inconvenient, and time-consuming, with treatment lasting throughout the lifetime of the individual. The majority of compliant patients can be treated successfully with conservative measures. [64, 65, 66]
In secondary lymphedema, the underlying etiology (ie, neoplasm, infection) should also be properly treated, in order to relieve the lymphatic obstruction.
A few pharmacologic therapies have been found to be effective in the treatment of lymphedema. For example, the benzopyrones (including coumarin and flavonoids), when combined with complex physical therapy, have been successful against the disease. Diuretics are not effective in treating lymphedema.
The disease burden of lymphedema is substantial, particularly in underdeveloped countries, with barriers including availability, affordability, and accessibility of bandages. [67] In Kenya, dermatologists and pharmacists are collaborating to develop a two-component compression bandage using locally available materials.
Hygiene and skin care
Appropriate skin care and debridement are stressed in the treatment of lymphedema, to prevent recurrent cellulitis or lymphangitis. [68]
Meticulous hygiene is necessary to remove keratinous debris and bacteria. Cleanse the skin regularly and dry thoroughly. Regular inspection is necessary to identify any open wounds or developing cellulitis. Bland skin moisturizers applied conservatively may ameliorate cracking and furrowing.
Physical therapy and compression
The first-line treatment for lymphedema is complex physical therapy. [4] This treatment is aimed at improving lymphedema with manual lymphatic drainage, massage, and exercise. It advocates the use of compression stockings (at a minimum of 40 mm Hg), [69] multilayer bandaging, or pneumatic pumps. Leg elevation is essential.
Other conservative therapies
Encourage patients to lose weight, avoid even minor trauma, and avoid constrictive clothing that might have a tourniquet effect. Encourage elevation of the affected extremity whenever possible, particularly at night. For lower extremity lymphedema, this may be accomplished by elevating the foot of the bed to an appropriate level.
Surgery
Surgical treatment is palliative, not curative, and it does not obviate the need for continued medical therapy. Moreover, it is rarely indicated as the primary treatment modality. Rather, surgical treatment is reserved for patients who do not improve with conservative measures or for cases in which the extremity is so large that it impairs daily activities and prevents successful conservative management.
A myriad of surgical procedures have been advocated for the treatment of lymphedema, reflecting a lack of clear superiority of one procedure over the others. Multiple physiologic and excisional techniques have been described. None of the physiologic techniques has clearly documented long-term favorable results; further evaluation is necessary. Moreover, many of the physiologic techniques also include an excisional component, making it difficult to distinguish between the 2 approaches.
Activity
Encourage patients to exercise after a graded support has been applied to the involved extremity.
Consultations
An oncologist should be consulted if a neoplasm is identified. Consultation with an infectious disease specialist is indicated for the treatment of recurrent cellulitis.
Compression Therapy
Patients should use compression garments continuously during the day. They may be removed at night when the extremity is elevated in bed, but they should be replaced promptly each morning. To encourage compliance, the elastic compression garments must fit appropriately. Garments should be custom fit when the extremity is decompressed, they should be comfortable, and they should not have a tourniquet effect. They should also have graduated compression that increases from distal to proximal on the affected extremity.
King suggested that toe bandaging may be a helpful treatment modality to prevent and manage edema involving the toes. [70]
Pneumatic pump compression
Intermittent pneumatic pump compression therapy may be instituted, on an outpatient basis or in the home. It provides sequential, active compression from distal to proximal, effectively milking the lymph from the extremity. This treatment is most appropriately used prior to fibrosclerotic evolution, which it assists in preventing. Contraindications to intermittent pneumatic pump compression therapy include congestive heart failure, deep vein thrombosis, and active infection.
Manual Treatment Techniques
In Europe, the best available nonsurgical therapy is manual lymphatic drainage according to the Vodder and/or Leduc techniques. Compression garments are essential between treatments. Similarly, other authors advocate manual massage of the affected extremity; this recruits collateral vessels, allowing the accumulated lymph to be drained into neighboring regions with normally functioning lymphatics.
Comparing treatments for breast-cancer related lymphedema, Gurdal et al found that the effectiveness of manual lymphatic drainage combined with the use of a compression bandage was similar to that for a combination of intermittent pneumatic compression and self-lymphatic drainage. Both combination treatments in the study produced a similar, significant reduction in total arm volume, as well as significant improvements on test scores assessing emotional functioning, fatigue, and pain. Only patients in the manual drainage/compression bandage group, however, seemed to show improvement in global health status and in functional and cognitive functioning test scores. [71]
A randomized trial showed that modified complex decongestive physiotherapy is effective for preventing lower extremity lymphedema in cervical cancer patients following laparoscopic radical hysterectomy with pelvic lymphadenectomy. [72]
Pharmacologic Therapy
Cellulitis
Even with excellent skin care, chronic cellulitis may occur. At the earliest signs of infection, institute topical or systemic antifungal or antimicrobial therapy to prevent the development of sepsis. Sometimes long-term treatment with antifungal and antibacterial treatments can result in a remission of the recurrent cellulitis (75-85%). Long-term, prophylactic treatment with antimicrobial agents such as penicillin, cephalexin, or erythromycin may be required in 15-25% of patients experiencing recurrent lymphangitis or cellulitis. [73, 74]
Filariasis
Filariasis has been treated with diethylcarbamazine and albendazole. [75] The combination of 2-week doxycycline with rifampicin may produce moderate macrofilaricidal activity against Wuchereria bancrofti. [28] Doxycycline itself may improve filarial lymphedema. [76] The mass administration of ivermectin and albendazole has proven effective for eliminating lymphatic filariasis in endemic areas, [77] however, with continued recognition that additional measures may be needed as it can spillover into Europe and North America. Moxidectin may provide longer microfilarial suppression compared with ivermectin and may prove better for onchocerciasis elimination. [78]
Benzopyrones
When combined with complex physical therapy, the benzopyrones (including coumarin and flavonoids) are a group of drugs that have been found to be successful in treating lymphedema. These drugs bind to accumulated interstitial proteins, inducing macrophage phagocytosis and proteolysis. The resulting protein fragments pass more readily into the venous capillaries and are removed by the vascular system.
The benzopyrones aid in decreasing excess edematous fluid, softening the limb, decreasing skin temperature, and reducing the number of secondary infections. Of note, however, is that hepatotoxicity has been associated with coumarin therapy.
Retinoids
Case reports have suggested that oral and topical retinoids can provide effective treatment of chronic lymphedematous changes (eg, elephantiasis nostra verrucosa [ENV]). These therapies are thought to help normalize keratinization and decrease inflammatory and fibrotic changes. [79, 80]
Topical agents
Topical emollients and keratolytics, such as ammonium lactate, urea, and salicylic acid, have been recommended to improve secondary epidermal changes.
Physiologic and Excisional Surgery
As previously mentioned, surgical treatment is palliative, not curative, and it does not obviate the need for continued medical therapy. Moreover, it is rarely indicated as the primary treatment modality, but is instead reserved for patients who do not improve with conservative measures or for cases in which the extremity is so large that it impairs daily activities and prevents successful conservative management. [81] Lymphaticovenular anastomosis surgery can be used to reduce lymphedema severity in selected patients. [82] Combining a lymphaticovenular anastomosis operation with complex physical therapy during the same hospitalization may provide a good combination therapy for advanced lymphedema. [83]
In general, surgical procedures are classified as physiologic or excisional. However, many physiologic techniques include an excisional component, making it difficult to distinguish between the 2 approaches. [84]
Physiologic surgery
Physiologic procedures attempt to improve lymphatic drainage. Multiple techniques have been described, including omental transposition, buried dermal flaps, enteromesenteric bridging, lymphangioplasty, and microvascular lympholymphatic anastomosis. [85] None of these techniques has clearly documented favorable long-term results. Further evaluation is necessary.
Rarely, venous-lymphatic anastomosis is performed in patients with severe lymphedema and a functioning venous system. Reports in the literature suggest that this procedure is effective only in cases of secondary lymphedema. Prophylactic lymphovenous anastomosis has been performed in patients undergoing extensive pelvic lymph node dissection who have a high risk of developing lymphedema.
Excisional surgery
Excisional techniques remove the affected tissues, thus reducing the lymphedema-related load. Some authors advocate suction-assisted removal of subcutaneous tissues, but this technique is difficult because of the extensive subcutaneous fibrosis that is present. Additionally, this approach does not reduce the skin envelope, and the lymphedema often rapidly recurs. Suction-assisted removal of subcutaneous tissue followed by excision of the excess skin envelope has no clear advantage over direct excisional techniques alone.
The Charles procedure is another quite radical excisional technique. This procedure involves the total excision of all skin and subcutaneous tissue from the affected extremity. The underlying fascia is then grafted, using the skin that has been excised. This technique is extreme and is reserved for only the most severe cases. Complications include ulceration, hyperkeratosis, keloid formation, hyperpigmentation, weeping dermatitis, and severe cosmetic deformity.
A variant of the Charles procedure, total superficial lymphangiectomy, involves debulking of the entire limb.
Van der Walt et al developed a modified Charles procedure in which negative-pressure dressing was employed following debulking surgery, with skin grafting delayed for 5-7 days. [86] In a report on 8 patients suffering from severe primary lymphedema who underwent the procedure, the authors reported that the patients experienced no major complications. Minor complications, including operative blood loss and, in 3 patients, the need for additional grafting, did occur.
Staged excision has become the option of choice for many authors. This procedure involves removing only a portion of skin and subcutaneous tissue, followed by primary closure. After approximately 3 months, the procedure is repeated on a different area of the extremity. This procedure is safe and reliable and demonstrates the most consistent improvement with the lowest incidence of complications.
Maggot debridement therapy for elephantiasis nostras verrucosa is effective, and, owing to increasing antimicrobial resistance, is gaining popularity. It can be used in conjunction with tangential surgical debridement. Hyperammonemia due to secretions with from maggots can occur. [87]
Preoperative details
Prior to surgery, appropriate documentation is necessary to evaluate the outcome of treatment. This includes photographic documentation as well as extremity measurements. Ideally, these measurements are of limb volume by water displacement, although some rely on circumferential measurements alone. Obtain measurements and photographs at the same time of day each time, document affected extremities and contralateral extremities, and preferably conduct documentation in the morning after extremity elevation in bed overnight.
Institute strict elevation and pneumatic compression, if available, 24-72 hours prior to surgery. This allows maximum excision to be performed. The extremity must also be free of infection at the time of surgery; a single dose of preoperative intravenous antibiotic is administered.
Intraoperative details
Surgery for removal of lymphedematous tissue includes the following steps:
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After the establishment of appropriate anesthesia, the operative field is sterilized and draped according to surgeon preference
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A pneumatic tourniquet is placed at the root of the extremity and insufflated after the extremity has been exsanguinated
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A longitudinal incision is made along the entire extremity, and skin flaps, 1.0-1.5 cm thick, are elevated
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Subcutaneous tissue is then excised, with care taken not to injure peripheral sensory nerves
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Some authors also excise a strip of deep fascia; however, this should not be performed around joints, because it may cause instability
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Once the subcutaneous excision is complete, redundant skin is resected; often, a strip that is 5-10 cm wide may be removed
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The wound is closed over suction drains
Postoperative care
Postoperatively, the extremity is immobilized in a splint and elevated; the patient is placed on strict bed rest.
Antibiotics may be continued until drain removal, according to surgeon preference. Drains are typically removed at 5-7 days postoperatively, as dictated by a decrease in drain output. Sutures are removed at 10-14 days and replaced by Steri-Strips.
The patient should be measured for a new compression garment when the new dimensions of the extremity have stabilized. After approximately 10 days, the patient may gradually begin dependency on the extremity with compression bandages or an elastic garment in place.
Postoperative follow-up
Once discharged from the hospital, the patient should be seen regularly in the outpatient clinic. Patients must wear compression garments continuously for 4-6 weeks; dependency on the involved extremity may be gradually increased at the discretion of the treating physician.
Once he or she has healed to physician satisfaction, the patient may return to a normal routine of elevation at night and compression garment therapy during the day.
Follow-up visits should include documentation of circumferential measurement or water displacement of the affected and contralateral extremities, as well as photographic documentation.
When staging procedures, allow approximately 3 months between procedures to allow complete healing of the initial operative site.
Prevention Following Breast Cancer Surgery
Results from a randomized, single-blind, controlled trial suggested that in trying to prevent arm lymphedema, manual lymph drainage with instructional guidelines and an exercise program does not provide significantly better results than an exercise program and guidelines alone do after axillary lymph node dissection for breast cancer. According to the investigators, triple therapy (manual drainage, guidelines, exercise) was not likely to produce medium to large effects in the short-term. [35, 88]
In contrast, however, a randomized, single-blind, clinical trial by Torres et al indicated that in women who have undergone breast cancer surgery, early physiotherapy may help to prevent postoperative secondary lymphedema for at least 1 year. The study included 116 women (patients who did or did not receive early physiotherapy) who had undergone breast cancer surgery involving dissection of the ancillary lymph nodes.
In the early physiotherapy group, treatment included manual lymph drainage, scar tissue massage, and progressive active and action-assisted shoulder exercises. At 1-year follow-up, the authors found that 25% of patients (14 patients) in the control group had developed secondary lymphedema, compared with 7% of patients (4 patients) in the early physiotherapy group. [89, 90]
One study has suggested that some patients have a genetic predisposition to develop lymphedema after breast cancer treatment. [91, 92] Other risk factors identified in this study were advanced cancer at the time of diagnosis, increased number of lymph nodes removed, and high body mass index.
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Lymphedema in a patient with hypertension, diabetes, and impaired cardiac function.
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Morbidly obese patient with lymphedema.
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The body quadrants of superficial lymph drainage.
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(1) Normal lymphatic flow in (a) deep systems and (b) superficial systems. Note the small collateral vessels interconnecting the 2 systems. (2) Lymphedema develops from obstruction, dilation of valves, valvular insufficiency, and subsequent reversal of lymphatic flow.
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Lymphatic system, anterior view.
